Neuronal membrane resting potential for large cells

Neuronal membrane resting potential for large cells

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I'm reading Medical Physiology by Boron and Boulpaep (a really terrific book). In the chapter Electrophysiology of the Cell Membrane, section Membrane Potential Is Generated by Ion Gradients, Not Directly by Ion Pumps, the text reads:

It may seem that the inside negative Vm originates from the continuous pumping of positive charges out of the cell by the electrogenic Na-K pump. The resting potential of large cells -- whose surface-to-volume ratio is so large that ion gradients run down slowly -- is maintained for a long time even when metabolic poisons block ATP-dependent energy metabolism. This finding implies that an ATP-dependent pump is not the immediate energy source underlying the membrane potential.

I totally get the main takeaway, that Vm results from the net accumulation of ion gradients, rather than the immediate consequences of the ion pumps. But I'm unclear on the phrase large cells -- whose surface-to-volume is so large that ion gradients run down slowly.

Presumably a cell with a large surface-to-volume ratio, like a long thin neuron, would have many ion channels which leak constitutively. So I'd expect the net ion conductance to be high, and gradients would run down quickly. But that contradicts the book's run down slowly point, so I'm confused.

Does passive diffusion play a role here? A long, thin cell would have slow passive ion diffusion, so is that why Vm would run down slowly?

Am I overthinking this?

What is the authors' point here?

In a typical neuron at rest, potassium is high inside the cell and low outside, with the opposite true for sodium. The membrane is mostly permeable to potassium. Let's ignore the other ions.

The resting potential in this situation will be something like -70 mV. Rest means that the net current flow is zero; however, there is still current: potassium is flowing out of the cell and sodium is flowing in. Therefore, if we turn off the sodium-potassium pump, over time, the concentration gradients will slowly equalize.

The authors are making an assumption that the current is roughly a function of membrane surface area: more membrane = more current. However, the "reservoir" of concentration imbalance is a function of volume: a bigger cell has more total potassium ions than a smaller cell.

Therefore, in a large cell, if the membrane potential is mostly driven by the concentration gradient, and it takes a long time for the concentration inside to equalize with the outside because the current is small relative to the volume, the membrane potential will only change slowly if you use a toxin to stop the sodium-potassium pump.

I don't think the authors are really intending to say anything special about large cells versus small ones, they are just setting up some assumptions under which their argument about the resting potential is going to be most evident. This is a bit like in a physics textbook where you read something like "assume a uniform spherical baseball."

The claim they are making: "the membrane potential is because of the concentration gradient, not the action of the pump itself" is true for all cellular membranes, not just in large cells. This particular piece of evidence they are referring to, however, is going to be most obvious in a large cell. That's all.

If you tried to do this experiment in a very small cell by turning off the pumps and watching the membrane potential, you might erroneously conclude that the pump was responsible for the membrane potential, but this would be a false conclusion caused by the concentration gradient equalizing too quickly. Instead you should test it in a big cell to see the effect more clearly.

In my personal opinion, this is not the best evidence to explain this feature, but it's a hard concept for many people to grasp and I suspect the authors of your text approach it in several different ways to find one that sticks.

Introduction to Neurophysiology

Neurophysiology is the branch of physiology dealing with the functions of the nervous system. ie The study of the functional properties of neurones, glia, and networks.

  • Historically it has been dominated by electrophysiology—the electrical recording of neuronal events ranging from the molar (the electroencephalogram, EEG) to the cellular (intracellular recording of the properties of single neurons).
  • As the neuron is an electrochemical machine, it is impossible to separate electrical events from the biochemical and molecular processes that bring them about.
  • Neurophysiologists today use techniques from chemistry (calcium imaging), physics (functional magnetic resonance imaging, fMRI), and molecular biology (site directed mutations) to study brain function. [1]

Below you will learn all about

  • Ion Channels
  • Resting Membrane and Action Potential
  • Neuromuscular Junction / Synapses
  • Nerve Conduction
  • Neurotransmitters, Receptors and Pathways

Neuro Scripts

Ion channels are important drug targets. A young team of researchers led by pharmacologist Anna Stary-Weinzinger from the Department of Pharmacology and Toxicology, University of Vienna investigated the opening and closing mechanisms of these channels: for the first time the full energy landscape of such a large protein (> 400 amino acids) could be calculated in atomic detail. The scientists identified a phenylalanine, which plays a key role for the transition between open and closed state. The time consuming calculations were performed using the high performance computer cluster (VSC), which is currently the fastest computer in Austria.

Recently, the results were published inPLOS Computational Biology.

Every cell of our body is separated from its environment by a lipid bilayer. In order to maintain their biological function and to transduce signals, special proteins, so called ion channels, are embedded in the membrane. Anna Stary-Weinzinger and Tobias Linder from the University of Vienna and Bert de Groot from the Max Planck Institute of Biophysical Chemistry in Göttingen identified a key amino acid (phenylalanine 114), which plays an essential role for opening and closing of these ion channels. A conformational change of phenylalanine triggers opening of the channels.

“These proteins are highly selective, they can distinguish between different ions such as sodium, potassium or chloride and allow ion flux rates of up to 100 million ions per seconds,” explains Stary-Weinzinger, leader of the research project and postdoc at the Department of Pharmacology and Toxicology of the University of Vienna. “These molecular switches regulate numerous essential body functions such as transduction of nerve signals, regulations of the heart rhythm or release of neurotransmitters. Slight changes in function, caused by replacement of single amino acids, can lead to severe diseases, such as arrhythmias, migraine, diabetes or cancer.”

Knowledge of ion channel function provides the basis for better drugs

Ion channels are important drug targets. 10 percent of current pharmaceuticals target ion channels. A detailed understanding of these proteins is therefore essential to develop drugs with improved risk-benefit profiles. An important basis for drug development is a detailed knowledge of the functional mechanisms of these channels. However, there are still many open questions especially the energy profile and pathway of opening and closure are far from being understood.

Computer simulations visualize ion channel movements

To watch these fascinating proteins at work, molecular dynamics simulations are necessary. Computational extensive calculations were performed with the help of the Vienna Scientific Cluster (VSC), the fastest high performance computer in Austria, a computer cluster operated by the University of Vienna, the Vienna University of Technology and the University of Natural Resources and Applied Life Sciences Vienna. With the help of VSC, the free energy landscape of ion channel gating could be investigated for the first time. The young researchers discovered that the open and closed channel states are separated by two energy barriers of different height.

Phenylalanine triggers conformational changes

Surprisingly, the dynamics of a specific amino acid, phenylalanine 114, are coupled to a first smaller energy barrier. “This side chain acts as molecular switch to release the channel from the closed state,” explains Tobias Linder, PhD student from the University of Vienna. After these local changes, the channel undergoes large global rearrangements, leading to a fully open state. This second transition from an intermediate to a fully open pore is accompanied by a large second energy barrier.

This research project is financed by the FWF-doctoral program “Molecular Drug Targets” (MolTag), which is led by Steffen Hering, Head of the Department of Pharmacology and Toxicology of the Faculty of Life Sciences, University of Vienna.

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Resting potential

Resting potential is largely determined by the difference concentration of K + ions and has a value of -70 to -90 mV, the cell's interior has a negative charge.

Action potential

If we introduce one electrode inside the axon and one to the cytoplasmic surface of the axon, hyperpolarization (in the case of negative internal electrodes) or depolarization (in the case of negative external) occurs.

If we increase the membrane potential to the threshold potential (in membrane with resting membrane potential, from -70mV to about -55 mV), nerve fiber responds with the emergence of an action potential (sudden opening voltage-gated sodium ion channels , thus allowing ions of sodium to enter through the membrane, causing the inside of the cells to become positive - there is transpolarization).

If the increment in the membrane potential doesn't reach "threshold potential", the sodium voltage-gated channel will not open. In this case, no action potential is generated.

In the next phase, the membrane again becomes permeable for potassium ions and the potential returns to resting value despite a slight hyperpolarization.


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Hernandez-Diaz S., and Levin, M., (2014), Alteration of bioelectrically-controlled processes in the embryo: a teratogenic mechanism for anticonvulsants, Reproductive Toxicology, 47: 111-114

Levin, M., (2014), Endogenous bioelectrical networks store non-genetic patterning information during development and regeneration, Journal of Physiology, 592(11): 2295–2305

Pai, V., and Levin, M., (2014), Bioelectric controls of stem cell function, Chapter 5 in F. Calegari and C. Waskow (Eds.), Stem Cells: From Basic Research to Therapy, Volume 1, CRC Press: Boca Raton, FL, p. 106-145
Amazon book

Lobikin, M., and Levin, M., (2014), Endogenous bioelectric cues as morphogenetic signals in vivo, Chapter 15 in D. Fels, M. Cifra, and F. Scholkmann (Eds), Fields of the Cell, Research Signpost: Kerala, India p. 283-302

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Sundelacruz, S., Levin, M., and Kaplan, D. L., (2013), Depolarization Alters Phenotype, Maintains Plasticity of Predifferentiated Mesenchymal Stem Cells, Tissue Engineering Part A, 19 (17-18): 1889-1908

Chernet, B., and Levin, M., (2013), Endogenous voltage potentials and the microenvironment: bioelectric signals that reveal, induce, and normalize cancer, Journal of Clinical and Experimental Oncology, S1: doi:10.4172/2324-9110.S1-002

Levin, M., (2013), Reprogramming cells and tissue patterning via bioelectrical pathways: molecular mechanisms and biomedical opportunities, Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 5(6): 657-676

Levin, M., (2013), Bioelectrical signaling has rich history, Physics Today, 66(9): 11

Chernet, B. T., and Levin, M., (2013), Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development, Disease Models & Mechanisms, 6(3): 595-607

Beane, W. S., Morokuma, J., Lemire, J. M., and Levin, M., (2013), Bioelectric signaling regulates head and organ size during planarian regeneration, Development, 140(2): 313-322

Tseng, A-S., and Levin, M., (2013), Cracking the bioelectric code: probing endogenous ionic controls of pattern formation, Communicative & Integrative Biology, 6(1): e22595

Adams, D. S., Tseng, A-S. and M. Levin, (2013), Light-activation of the Archaerhodopsin H+ pump reverses age-dependent loss of vertebrate regeneration: sparking system-level controls in vivo, Biology Open, 2(3): 306-313

Pai, V. P., Vandenberg, L. N., Blackiston, D. J., and Levin, M., (2012), Neurally-derived tissues in Xenopus laevis embryos exhibit a consistent bioelectrical left-right asymmetry, Stem Cells International, 2012: 353491, doi:10.1155/2012/353491

Lobikin, M., Chernet, B., Lobo, D., and Levin, M., (2012), Resting potential, oncogene-induced tumorigenesis, and metastasis: the bioelectric basis of cancer in vivo, Physical Biology, 9(6): 065002

Tseng, A.-S., and Levin, M., (2012), Transducing bioelectrical signals into epigenetic pathways during tadpole tail regeneration, Anatomical Record, 295(10): 1541-1551

Adams, D. S., and Levin, M., (2013), Endogenous Voltage Gradients as Mediators of Cell-Cell Communication: Strategies for Investigating Bioelectrical Signals During Pattern Formation, Cell and Tissue Research, 352(1):95-122

Levin, M., and Stevenson, C., (2012), Regulation of Cell Behavior and Tissue Patterning by Bioelectrical Signals: challenges and opportunities for biomedical engineering, Annual Reviews in Biomedical Engineering, 14: 295-323

Adams, D. S., and Levin, M., (2012), General principles for measuring resting membrane potential and ion concentration using fluorescent bioelectricity reporters, Cold Spring Harbor Protocols, 2012(4): 385-397 [cover]

Adams, D. S., and M. Levin, (2012), Measuring resting membrane potential using the fluorescent voltage reporters and , CSHL Protocols, doi: 10.1101/pdb.prot067702

Levin, M., (2012), Molecular bioelectricity in developmental biology: new tools and recent discoveries, BioEssays, 34(3): 205-217 [cover]

Pai, V., Aw, S., Shomrat, T., Lemire, J. M., and Levin, M., (2012), Transmembrane voltage potential controls embryonic eye patterning in Xenopus laevis, Development, 139(2): 313-323

Blackiston, D., Adams, D. S., Lemire, J. M., Lobikin, M., and Levin, M., (2011), Transmembrane potential of GlyCl-expressing instructor cells induces a neoplastic-like conversion of melanocytes via a serotonergic pathway, Disease Models and Mechanisms, 4(1): 67-85

Beane, W. S., Morokuma, J., Adams, D. S., and Levin, M., (2011), A chemical genetics approach reveals H,K-ATPase-mediated membrane voltage is required for planarian head regeneration. Chemistry & Biology,

Lange, C., Prenninger, S., Knuckles, P., Taylor, V., Levin, M., and Calegari, F., (2011), The H(+) vacuolar ATPase maintains neural stem cells in the developing mouse cortex, Stem Cells and Development, 20(5): 843-850

Levin, M. (2011), Endogenous bioelectrical signals in development, regeneration, and neoplasm, in Topical Talks: The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London.

Levin, M. (2011), Left-Right Asymmetry in Embryonic Development: How epigenetic, biophysical forces and gene activity interplay to determine a major embryonic axis, in Topical Talks: The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London.

Levin, M., (2011), Endogenous Bioelectric Signals as Morphogenetic Controls of Development, Regeneration, and Neoplasm, in The Physiology of Bioelectricity in Development, Tissue Regeneration, and Cancer, C. Pullar (Ed.), CRC Press: Boca Raton, FL, p. 39-89
Available here

Levin, M., (2011), The wisdom of the body: future techniques and approaches to morphogenetic fields in regenerative medicine, developmental biology, and cancer. Regenerative Medicine, 6(6): 667-673

Aw, S., Koster, J., Pearson, W., Nicols, C., Shi, N. Q., Carneiro, K., and Levin, M., (2010), The ATP-sensitive K+-channel (KATP) controls early left-right patterning in Xenopus and chick embryos. Developmental Biology, 346: 39-53

Tseng, A-S., Beane, W. S., Lemire, J. M., Masi, A., and M. Levin, (2010), Induction of vertebrate regeneration by a transient sodium current, Journal of Neuroscience, 30(39): 13192-13200

Zhang, Y., and M. Levin, (2009), Particle tracking model of electrophoretic morphogen movement reveals stochastic dynamics of embryonic gradient, Developmental Dynamics, 238(8): 1923-1935

Levin, M. (2009), Bioelectric mechanisms in regeneration: Unique aspects and future perspectives. Seminars in Cell and Developmental Biology, 20: 543-556

Levin, M., Sundelacruz, S., Levin M., Kaplan, D. L., (2009), Role of membrane potential in the regulation of cell proliferation and differentiation, Stem Cell Reviews, 5(3): 231-46

Blackiston, D. J., K. McLaughlin, and Levin, M., (2009), Bioelectric controls of cell proliferation: ion channels, membrane voltage, and the cell cycle, Cell Cycle, 8(21): 3527-3536

Morokuma, J., Blackiston, D., and Levin, M., (2008), KCNQ1 and KCNE1 K+ channel components are involved in early left-right patterning in Xenopus embryos, Cellular Physiology and Biochemistry, 21: 357-372

Morokuma, J., Blackiston, D., Adams, D. S., Seebohm, G., Trimmer, B., and Levin, M., (2008), Modulation of potassium channel confers a hyper-proliferative invasive phenotype on embryonic stem cells, Proceedings of the National Academy of Sciences of the United States, 105(43): 16608-16613

Sundelacruz, S., M. Levin, and D. L. Kaplan, (2008), Membrane potential controls adipogenic and osteogenic differentiation of mesenchymal stem cells, PLoS One, 3(11): e3737, 1-15

Oviedo, N. J., Nicolas, C. L., Adams, D. S., and Levin, M., (2008), Live imaging of planarian membrane potential using DiBAC4(3). Cold Spring Harbor Protocols, doi:10.1101/pdb.prot5055

Adams, D. S., Masi, A., and Levin, M. (2007), H+ Pump-dependent changes in membrane voltage are an early mechanism necessary and sufficient to induce Xenopus tail regeneration. Development, 134: 1323-1335

Aw, S., Adams, D. S., Qiu, D., and Levin, M., (2007), H,K-ATPase protein Localization and Kir4.1 function reveal concordance of three axes during early determination of left-right asymmetry, Mechanisms of Development, 125: 353-372

Levin, M., (2007), Large-Scale Biophysics: Ion Flows and Regeneration. Trends in Cell Biology, 17(6): 261-270

Hibino, T., Ishii, Y., Levin, M., and Nishino, A., (2006), Ion flow regulates left-right asymmetry in sea urchin development. Development, Genes and Evolution, 216(5): 265-76

Shimeld, S. M., and Levin, M., (2006), Evidence for the regulation of left-right asymmetry in Ciona intestinalis by ion flux. Developmental Dynamics, 235(6): 1543-1553

Adams, D. S., Robinson, K.R., Fukumoto, T., Yuan, S., Albertson, R. C., Yelick, P., Kuo, L., McSweeney, M., Levin, M., (2006), Early, H+-V-ATPase-dependent proton flux is necessary for consistent left-right patterning of non-mammalian vertebrates. Development, 133: 1657-1671

Esser, A. T., Smith, K. C., Weaver, J. C., and Levin, M., (2006), Mathematical Model of Morphogen Electrophoresis through Gap Junctions. Developmental Dynamics, 235(8): 2144-2159

Adams, D. S., and Levin, M., (2006), Inverse Drug Screens: a rapid and inexpensive method for implicating molecular targets. Genesis, 44: 530-540

Adams, D., and Levin, M., (2006), Strategies and techniques for investigation of biophysical signals in patterning, in Analysis of Growth Factor signaling in Embryos, M. Whitman and A. K. Sater eds., pp. 177-264, Methods in Signal Transduction Series, CRC Press

M. Levin, (2003), Bioelectromagnetics in morphogenesis. Bioelectromagnetics, 24(5): 295-315

M. Levin, (2003), Motor protein control of ion flux is an early step in embryonic Left-Right asymmetry. BioEssays, 25(10): 1002-1010

Levin, M., Thorlin, T., Robinson, K., Nogi, T., and Mercola, M., (2002), Asymmetries in H+/K+-ATPase and cell membrane potentials comprise a very early step in left-right patterning, Cell, 111(1): 77-89

J. Rutenberg, S. M. Cheng, and M. Levin, (2002), Early embryonic expression of ion channels and pumps in chick and Xenopus development. Developmental Dynamics, 225(4): 469-484

S. M. Cheng, I. Chen, and M. Levin, (2002), Katp channel activity is required for hatching in Xenopus. Developmental Dynamics, 225(4): 588-591

Levin, M., (1999), Endogenous electromagnetic fields and radiations in regeneration, development, and neoplasm, Proceedings of the First World Congress on the Effects of Electricity and Magnetism in the Natural World, Madeira, Portugal

Levin, M., and Ernst, S. G., (1997), Applied DC magnetic fields cause alterations in the time of cell divisions and developmental abnormalities in early sea urchin embryos, Bioelectromagnetics, 18(3): 255-263

Levin, M., and Ernst, S. G., (1995), Applied AC and DC Magnetic Fields Cause Alterations in the Mitotic Cycle of Early Sea Urchin Embryos, Bioelectromagnetics, 16(4): 231-240

Levin, Michael, Current and potential applications of bioelectromagnetics in medicine, (1993), ISSEEM Journal, 4(1): 77-87

Large LNv spontaneous tonic and burst pattern action potentials are abolished by treatment with pharmacological blockers of voltage-gated sodium and calcium channels

The observed threshold of activation of spontaneous action potential firing for large LNv neurons is close to the reported value for the Drosophila voltage-gated sodium channel para (O'Dowd and Aldrich 1988 Wicher et al. 2001), suggesting that the depolarizing phase of the large LNv action potential is mediated by the opening of voltage-dependent sodium channels. Bath application of 100 nM tetrodotoxin (TTX, a voltage-gated sodium channel blocker) rapidly abolishes spontaneous action potential firing in large LNvs (Fig. 2, AC and Supplemental Fig. S1, A1–3).1 In contrast to the profound suppression of spontaneous action potential firing, 100 nM TTX treatment has no effect on mean resting potential (Fig. 2, AC and Supplemental Fig. S1A1–3). TTX suppression of spontaneous action potential firing is relatively resistant to washout, but two of six cells tested showed discernible washout (Fig. 2C). The poor washout of TTX is consistent with the high affinity of this blocker (Gitschier et al. 1980). TTX treatment also dampens low-frequency membrane oscillations (Fig. 2B and Supplemental Fig. S1A2). These data demonstrate that the spontaneous action potentials require flux of sodium through voltage-gated channels and that sodium channel activity also contributes to generation of slow-wave oscillations (Fig. 2, A and B, Supplemental Fig. S1A1–3).

FIG. 2.Voltage-gated sodium and calcium channel blockers abolish the spontaneous AP firing of large LNvs. A: firing of a representative large LNv measured in whole cell current clamp at 0-pA holding membrane current in control perfusion solution. B: recording from the same cell in the presence of 100 nM tetrodotoxin (TTX). The application of 100 nM TTX completely abolishes large LNv spontaneous APs (n = 6). C: example trace showing recovery of spontaneous firing after washout of TTX (2/6 cells). D: representative long-duration whole cell current-clamp recording of one large LNv at 0-pA holding current in control solution during washin and washout of 2 mM CoCl2 shows state modulation of a large LNv showing burst firing becoming tonic and then silent with 2 mM CoCl2 washin followed by washout recovery to tonic and then burst firing pattern (x-axis shows time in seconds, n = 6). D1–6: detail of traces sampled from the above trace for 20 s. D1: burst firing before CoCl2 washin, (D2) initial broadening of slow-wave oscillation and crests of firing in response to CoCl2 washin, (D3) during transition from tonic to silent, (D4) silent phase, (D5) transition from silent to tonic showing recovery of large LNv spontaneous firing after CoCl2 washout, and (D6) transition from tonic to burst firing showing complete washout.

To determine whether voltage-gated calcium channels also contribute to spontaneous (and evoked) action potentials and or low-frequency membrane potential oscillations, the effect of bath-applied 2 mM CoCl2 on large LNv activity was tested. We subsequently measured whether the effects of 2 mM CoCl2 on large LNv activity are reversible by washout with fresh bath solution. Five of six cells examined in whole cell recordings were initially burst firing cells and one of the six cells was tonic firing before application of CoCl2. All burst firing cells initially show broader crests of firing on slower-frequency membrane potential oscillations along with more depolarized membrane potential in response to CoCl2 washin (n = 5 Fig. 2D compare D1 and D3). All five cells then transitioned from slow burst firing to tonic firing (Fig. 2, D1 and D3). For two of the five initial burst-firing cells, this tonic firing pattern persisted throughout CoCl2 treatment. In the three other initial burst-firing cells, CoCl2 caused the cells to transition from tonic firing to silent (no firing) state (Fig. 2, D, D3, and D4). On washout of CoCl2, in the three cells that were silenced by CoCl2, spontaneous tonic firing appeared first followed by recovery of bursting pattern (Fig. 2, D and D5), whereas the two cells that remained at tonic firing during CoCl2 washin transitioned back to burst firing during the washout (Fig. 2, D and D6). Similarly, the single large LNv that was initially tonic firing became silent in response to CoCl2 washin followed by a recovery back to tonic firing following CoCl2 washout. These results indicate that the firing pattern in large LNv is state modulated, and that state transitions between firing patterns in response to CoCl2 washin and washout behave in the sequence: from burst firing to tonic firing to silent with CoCl2 washin and recovery from silent to tonic firing to burst firing with CoCl2 washout (in some cases, cells “stall” at intermediate transition states, but they do not appear to bypass any intermediate transition states).

CoCl2 application also dampens high-amplitude, slow-frequency oscillations in membrane potential that is especially apparent in burst firing cells (Fig. 2, D and D4). Three of six cells showed significant depolarization of membrane potential on CoCl2 application, whereas two others did not show consistent significant change during CoCl2 application and one cell was slightly hyperpolarized. The ability of some neurons to continue firing in the presence of 2 mM CoCl2 and the ability of those that were silenced by CoCl2 application to fire action potentials when injected with depolarizing current (Supplemental Fig. S2) demonstrate that action potentials in large LNvs do not require activation of voltage-gated calcium channels. However, activity of these channels does modulate the firing pattern and firing rate of the neurons.

Types of synapses

There are two types of synapses:

Electrical synapses

In electrical synapses, two neurons are connected through channel proteins for transmitting a nerve impulse. The nerve impulse travels across the membrane of the axon in the form of an electrical signal. The signal is transmitted in the form of ions and therefore it is much faster than chemical synapses.

In electrical synapses, the synaptic gap is about 0.2nm which also favors faster nerve impulse conduction.

Chemical synapses

CNS and Nerve Impulse

Neurons help in transmitting signals in the form of a nerve impulse from the Central nervous system to the peripheral body parts. Neurons are a complex network of fibers that transmit information from the axon ending of one neuron to the dendrite of another neuron. The signal finally reaches the target cell where it shows a response.

In conducting nerve impulse, the following play a major role:

  • Axon- Helps in the propagation of nerve impulses to the target cell.
  • Dendrites- Receive the signals from the axon ends.
  • Axon Ending- Acts as a transmitter of signals.

Axon plays a major role in the process by transmitting signals in the form of nerve impulses via synapses to the target cells. The neuron is responsible for transferring signals to three target cells:

And this results in the contraction of muscle, secretion by glands and helps neurons to transmit action potential.


The brain is possibly the most fascinating part of the human body.

We share a lot of DNA, with other life forms.

We share a lot of Life processes, and organs, with other life forms.

If there is one organ, which differentiates us significantly,

from other life forms, it is the brain.

Human beings are endowed with the most amazingly advanced,

It is our advanced brain which makes us, the most important species in the planet.

The brain can be considered as an information processing,

and decision making centre of the human body.

All the thinking that we do, happens in the brain.

It is the seat of consciousness.

The brain also performs another critically important function.

The brain regulates and manages, all the life processes in the body.

Our breathing, our heart rate, our blood pressure etc,

are all controlled, by our brain.

This control of metabolic processes, or life processes, is automatic.

We are not conscious of the management of life processes.

For example, we don’t have to think about breathing, heart rate etc.

It happens automatically, even when we are asleep.

The fact that this process, is automatic, in no way,

reduces the importance of this function.

We need our brain to live.

We need to live, in order to think.

The thinking capability of human beings, is far superior to that of any animal.

Our intelligence is so superior, animal intelligence is not even comparable to ours.

The regions in the brain, capable of high level thinking,

is present only in the human brain.

The basic unit of a human brain, is the neuron.

All the information processing, that happens in the brain,

The brain is a collective organ, of billions of neurons.

It is estimated that the brain, has about hundred billion neurons.

Each neuron in the brain, is connected to hundreds and thousands,

All the information processing that happens, in the brain,

is interrelated in some way.

It is estimated that there are about hundred trillion connections in the brain.

It is these connections, that ultimately result in a process, we call thinking.

The brain can be referred to as a connectome, of neurons.

The connectome can also be thought of as the wiring circuit of the brain.

Memory, an important functionality, is organised in the Brain.

Even a feeling, such as anger, originates in the Brain.

The states of mind, being alert, motivated, or sleepy comes from the Brain.

It is the brain which helps us understand, and solve complex problems.

It is the brain which helps us invent all the wonderful things,

which we take for granted.

It is this connectome, which endows us with our superior intelligence.

This also makes, the brain a complex organ.

There are certain areas of the brain, which are specialised, in certain functions.

For example, there are special areas to process visual information,

All the areas of the brain, are however closely interrelated.

This makes the brain, a fascinatingly complex organ.

It also makes it a exciting subject for studying.

The brain is connected, to our whole body, via nerves.

Just like the heart is connected to the whole body, via blood vessels,

the brain is connected to the whole body, via nerves.

Nerve fibres carry signals, or information from and to the brain.

Afferent nerve fibres, carry information, from all over the body, to the brain.

Efferent nerve fibres, carry information, from the brain, to the body.

The nerves which emanate from the spine, and reach out to all parts of the body,

constitutes the peripheral nervous system.

Using the nerves to communicate,

the brain is able to manage, all the life processes of the body.

This is also the way, that the brain, gives instructions to all our skeletal muscles.

This enables us to consciously control our skeletal muscles.

This control helps us to perform day to day activities.

It is this control which helps us walk, talk, smile, play, work and dance.

All the nerves in the body, are collectively referred to as the nervous system.

The brain works closely with, and is strongly integrated with the nervous system.

The basic unit of the nervous system, and the brain, is the neuron.

In the nervous system, the neurons play the role of carrying signals,

We can say that the neuron is the building block, of the brain and nervous system.

All the neurons in the brain, and the nervous system,

have the same basic functionality.

This makes it worth while to understand the functioning of the neuron.

Throughout this module we will use examples, to understand concepts.

The examples and the values used, will be typical.

The examples help us understand the concepts.

However, we should bear in mind, that there could be variations and exceptions.

The neuron, is a living cell, like other cells in the body.

The neuron is a specialised cell.

The neuron is similar in structure, to other typical cells in the body.

It has a nucleus, and the same DNA, found in other cells.

It has mitochondria, which generates energy for a cell.

The neuron requires nutrients like other cells.

It has all other basic components of a living cell.

The neuron cell specialises, in the function of the nervous system.

Information transmission, and processing are the basic functions of the nervous system.

Most of the information processing takes place in the brain.

Signal transmission is taken care of by the nerves.

Communicating a signal to one or more neurons, is the most important function,

Inside the neuron, the signals are electrical signals.

A neuron typically communicates with another neuron,

in the peripheral nervous system, in the body.

A neuron communicates with hundreds and thousands,

of other neurons in the brain.

A neuron does not make physical contact, with another neuron.

A gap exists between a neuron ending, and the next neuron.

This gap is called the synapse.

To communicate across the synapse, the neuron uses chemical signals.

The chemical signals, generate a new electrical signal in the next neuron.

Dendrites are a series of out growths, from the cells body, or soma.

Neurons have multiple dendrites.

Each Dendrites have many branches, just like a tree.

The dendrites are the sites, for the specialised junctions, for receipt of signals.

The dendrites are the in gates, for the neuron.

The dendrites receive signals, from other neurons.

Dendrites enable many other neurons to connect with it.

The ability of one neuron to connect with many other neurons,

is critical to the functioning of the neuron, specially in the brain.

Neurons thus are specially designed, to connect with hundreds and thousands,

The cell body of a neuron, is called as the soma.

The soma is a living cell, like other cells.

It breathes in oxygen, and breathes out carbon dioxide.

It takes in nutrition, and gives out waste products.

The nucleus contains the same DNA, like other cells.

The DNA along with other genetic machinery can synthesise, many proteins.

The soma has the capability to generate energy.

The currency for energy is ATP.

Energy in the form of ATP, is essential for the cell.

Even a neuron at rest, requires expenditure of energy.

The brain which is comprised mostly of neurons,

consumes a surprisingly large amount of energy.

It is estimated that about 20% of the energy we consume,

The soma is enclosed by a cell membrane.

The cell membrane comprises of a phospholipid layer.

A phospholipid is a bio chemical, with a phosphate and lipid component.

The phosphate component is water loving, or hydrophilic.

The lipid component is water averse, or hydrophobic.

The inside and outside of the soma, has watery fluids.

Two phospholipid compound join together to form the unit of a cell membrane.

The lipid components face each other, and form the inner layer, of the membrane.

The phosphate component form the outer and inner layers, of the membrane.

The outer and inner layers are comfortable with the extra cellular,

and intra cellular fluids.

The lipid middle layer of the membrane, being hydrophobic, separates the extracellular,

and intracellular fluids and organelles.

The membrane acts as a container for the cell.

The membrane is selectively permeable to certain kinds of substances.

Charged particles or ions, are called polar molecules.

The membrane is specially impermeable to polar molecules.

The membrane prevents the free movement, of ions across it.

Neuron functionality requires the transfer of ions, across the membrane.

To enable this ion transport, the membrane has embedded proteins.

These special proteins, acts as channels and mechanisms,

to transport ions, across the membrane.

The inside of the cell membrane, is the intra cellular space.

The outside of the cell membrane, is the extra cellular space.

There are more positively charged ions, in the outside, or extra cellular space.

This causes the outside to be more positive.

There are less positively charged ions, in the inside, or intra cellular space.

This causes the inside to be less positive, or relatively negative.

This results in an electrical potential, to be created, across the cell membrane.

Membrane potentials are measured, relative to the inside of the membrane.

Neurons, even at rest, have a negative electrical potential.

Membrane potential, is the key to the functioning of the neuron.

Changes in the membrane potential results in a signal being generated.

This signal is called as the action potential.

Movement of the action potential, causes the signal to be transmitted.

Neurons are involved in receiving, processing and transmitting, of electrical signals.

Neurons receive signals, from other neurons, through their dendrites.

If the incoming signal is weak, the neuron will not respond to the signal.

There is a minimum signal strength, that is required,

This minimum level is called, as the threshold.

If the incoming signal strength, reaches threshold, or exceeds it,

the receiving neuron will get activated.

The soma receives signals from many dendrites.

Dendrites are just extensions of the soma.

Dendrites effectively increase the exposed surface area of the cell membrane,

This helps the neuron to receive signals from many other neurons, or cells.

The effective signal that is received, by a neuron,

is the sum of all the signals received by the neuron.

The signal strength has to reach threshold, to activate a neuron.

This threshold can be reached, by the sum of all the individual signals.

A number of weak signals, receive together, can create a signal strong enough,

to activate the receiving neuron.

This is an important concept, in understanding the functioning of a neuron.

Sustained Depolarization of the Resting Membrane Potential Regulates Muscle Progenitor Cell Growth and Maintains Stem Cell Properties In Vitro

It is important to maintain the myogenic properties of muscle progenitor cells (MPCs) during in vitro expansion for stem cell therapies and tissue engineering applications. Controlling cell fate for biomedical interventions will require insight on all aspects that influence cellular properties. The resting membrane potential (Vmem) has proven to be a key parameter involved in cell proliferation, migration and differentiation. This current work is focused on elucidating the impact of sustained depolarization on MPC growth and differentiation in vitro. Cultures were treated with either potassium gluconate or the sodium-potassium pump blocker ouabain and evaluated for proliferation, DNA content using propidum iodide staining, and differentiation. Cell proliferation measurements showed a modest stimulatory effect at certain concentration ranges for each agent, but higher concentrations of potassium gluconate strongly inhibited growth in a dose dependent manner. Cell cycle analysis with flow cytometry demonstrated an increase in the number of cells in S phase, but increasing concentrations of potassium gluconate arrested cells at G1. Immunostaining, Western blot analysis and light microscopy revealed that potassium gluconate exposure delayed cell fusion and maintained a higher population of cells expressing the muscle stem cell marker Pax7. The impairment on cell fusion was transient and myotube formation recovered after the treatments were removed. Taken together, this work suggests that transmembrane voltage gradients can be used as a powerful regulator of MPC properties in vitro. Examination of how these physiological parameters modulate cell behavior will reveal a new set of tools that can be capitalized on in tissue engineering and regenerative medicine.

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Action Potential

Action potentials are the electrical pulses that allow the transmission of information within nerves. An action potential represents a change in electrical potential from the resting potential of the neuronal cell membrane, and involves a series of electrical and underlying chemical changes that travel down the length of a neural cell (neuron). The neural impulse is created by the controlled development of action potentials that sweep down the body (axon) of a neural cell.

There are two major control and communication systems in the human body, the endocrine system and the nervous system. In many respects, the two systems compliment each other. Although long duration effects are achieved through endocrine hormonal regulation, the nervous system allows nearly immediate control, especially regulation of homeostatic mechanisms (e.g., blood pressure regulation).

The neuron cell structure is specialized so that at one end, there is a flared structure termed the dendrite. At the dendrite, the neuron is able to process chemical signals from other neurons and endocrine hormones. If the signals received at the dendritic end of the neuron are of a sufficient strength and properly timed, they are transformed into action potentials that are then transmitted in a "one-way" direction (unidirectional propagation) down the axon.

In neural cells, electrical potentials are created by the separation of positive and negative electrical charges that are carried on ions (charged atoms) across the cell membrane. There are a greater number of negatively charged proteins on the inside of the cell, and unequal distribution of cations (positively charged ions) on both sides of the cell membrane. Sodium ions (Na+) are, for example, much more numerous on the outside of the cell than on the inside. The normal distribution of charge represents the resting membrane potential (RMP) of a cell. Even in the rest state there is a standing potential across the membrane and, therefore, the membrane is polarized (contains an unequal distribution of charge). The inner cell membrane is negatively charged relative to the outer shell membrane. This potential difference can be measured in millivolts (mv or mvolts). Measurements of the resting potential in a normal cell average about 70 mv.

The standing potential is maintained because, although there are both electrical and concentration gradients (a range of high to low concentration) that induce the excess sodium ions to attempt to try to enter the cell, the channels for passage are closed and the membrane remains almost impermeable to sodium ion passage in the rest state.

The situation is reversed with regard to potassium ion (K+) concentration. The concentration of potassium ions is approximately 30 times greater on the inside of the cell than on the outside. The potassium concentration and electrical gradient forces trying to move potassium out of the cell are approximately twice the strength of the sodium ion gradient forces trying to move sodium ions into the cell. Because, however, the membrane is more permeable to potassium passage, the potassium ions leak through he membrane at a greater rate than sodium enters. Accordingly, there is a net loss of positively charges ions from the inner part of the cell membrane, and the inner part of the membrane carries a relatively more negative charge than the outer part of the cell membrane. These differences result in the net RMP of &minus70mv.

The structure of the cell membrane, and a process termed the sodium-potassium pump maintains the neural cell RMP. Driven by an ATPase enzyme, the sodium potassium pump moves three sodium ions from the inside of the cell for every two potassium ions that it brings back in. The ATPase is necessary because this movement or pump of ions is an active process that moves sodium and potassium ions against the standing concentration and electrical gradients. Equivalent to moving water uphill against a gravitational gradient, such action requires the expenditure of energy to drive the appropriate pumping mechanism.

When a neuron is subjected to sufficient electrical, chemical, or in some cases physical or mechanical stimulus that is greater than or equal to a threshold stimulus, there is a rapid movement of ions, and the resting membrane potential changes from &minus70mv to +30mv. This change of approximately 100mv is an action potential that then travels down the neuron like a wave, altering the RMP as it passes.

The creation of an action potential is an "all or none" event. Accordingly, there are no partial action potentials. The stimulus must be sufficient and properly timed to create an action potential. Only when the stimulus is of sufficient strength will the sodium and potassium ions begin to migrate done their concentration gradients to reach what is termed threshold stimulus and then generate an action potential.

The action potential is characterized by three specialized phases described as depolarization, repolarization, and hyperpolarization. During depolarization, the 100mv electrical potential change occurs. During depolarization, the neuron cannot react to additional stimuli and this inability is termed the absolute refractory period. Also during depolarization, the RMP of &minus70mv is reestablished. When the RMP becomes more negative than usual, this phase is termed hyperpolarization. As repolarization proceeds, the neuron achieves an increasing ability to respond to stimuli that are greater than the threshold stimulus, and so undergoes a relative refractory period.

The opening of selected channels in the cell membrane allows the rapid movement of ions down their respective electrical and concentration gradients. This movement continues until the change in charge is sufficient to close the respective channels. Because the potassium ion channels in the cell membrane are slower to close than the sodium ion channels, however, there is a continues loss of potassium ion form the inner cell that leads to hyperpolarization.

The sodium-potassium pump then restores and maintains the normal RMP.

In demyelinated nerve fibers, the depolarization induces further depolarization in adjacent areas of the membrane. In myelinated fibers, a process termed salutatory conduction allows transmission of an action potential, despite the insulating effect of the myelin sheath. Because of the sheath, ion movement takes place only at the Nodes of Ranvier. The action potential jumps from node to node along the myelinated axon. Differing types of nerve fibers exhibit different speed of action potential conduction. Larger fibers (also with decreased electrical resistance) exhibit faster transmission than smaller diameter fibers).

The action potential ultimately reaches the presynaptic portion of the neuron, the terminal part of the neuron adjacent to the next synapse in the neural pathway). The synapse is the gap or intercellular space between neurons. The arrival of the action potential causes the release of ions and chemicals (neurotransmitters) that travel across the synapse and act as the stimulus to create another action potential in the next neuron.

Watch the video: Membrane Potential, Equilibrium Potential and Resting Potential, Animation (February 2023).