*

*
*
 
*

Chapter 1: Resting Potentials and also Action Potentials

John H. Byrne, Ph.D., Department of Neurobiology and Anatomy, McGovern Medical School Revised 01 July 2021

*
*

Video of lecture

In spite of the huge complexity of the brain, it is possible to obtain an knowledge of its function by paying attention to 2 major details:

First, the methods in which individual neurons, the components of the nervous mechanism, are wired together to geneprice behavior. Second, the biophysical, biochemical, and also electrophysiological properties of the individual neurons.

A excellent place to begin is through the components of the nervous system and also just how the electric properties of the neurons endow nerve cells through the capability to procedure and also transmit indevelopment.

Video of lecture

1.1 Introduction to the Action Potential


Figure 1.1 Tap the colored circles (light stimulus) to activate.

You are watching: Why does the threshold increase when the interval between the stimuli decreases?


Theories of the encoding and also transmission of information in the nervous system go earlier to the Greek doctor Galen (129-210 AD), that suggested a hydraulic system through which muscles contract bereason liquid flowing into them from hollow nerves. The fundamental theory hosted for centuries and also was further elaborated by René Descartes (1596 – 1650) that argued that pet spirits flowed from the brain through nerves and then to muscles to produce motions (See this animation for modern interpretation of such a hydraulic concept for nerve function). A significant paradigm transition arisen with the pioneering occupational of Luigi Galvani that found in 1794 that nerve and muscle might be set off by charged electrodes and also suggested that the nervous mechanism attributes through electrical signaling (see this computer animation of Galvani"s experiment). However before, there was dispute among scholars whether the electrical energy was within nerves and also muscle or whether the nerves and also muscles were sindicate responding to the harmful electric shock by means of some intrinsic nonelectrical system. The issue was not resolved till the 1930s with the breakthrough of modern-day electronic amplifiers and also recording devices that allowed the electric signals to be taped. One example is the pioneering occupational of H.K. Hartline 80 years earlier on electric signaling in the horseshoe crab Limulus . Electrodes were inserted on the surchallenge of an optic nerve. (By placing electrodes on the surchallenge of a nerve, it is feasible to obtain an indication of the changes in membrane potential that are arising between the outside and inside of the nerve cell.) Then 1-s duration flashes of light of differed intensities were presented to the eye; first dim light, then brighter lights. Very dim lights developed no changes in the task, but brighter lights created tiny repeated spike-like occasions. These spike-favor occasions are called activity potentials, nerve impulses, or periodically simply spikes. Action potentials are the basic occasions the nerve cells use to transmit information from one location to one more.

1.2 Features of Action Potentials

The recordings in the number over illustrate three exceptionally vital attributes of nerve action potentials. First, the nerve activity potential has actually a brief duration (about 1 msec). Second, nerve action potentials are elicited in an all-or-nothing fashion. Third, nerve cells code the intensity of information by the frequency of activity potentials. When the intensity of the stimulus is enhanced, the size of the activity potential does not end up being larger. Rather, the frequency or the variety of activity potentials boosts. In general, the greater the intensity of a stimulus, (whether it be a light stimulus to a photoreceptor, a mechanical stimulus to the skin, or a stretch to a muscle receptor) the greater the number of action potentials elicited. Similarly, for the motor device, the higher the number of activity potentials in a motor neuron, the greater the intensity of the contraction of a muscle that is innervated by that motor neuron.

Action potentials are of good importance to the functioning of the brain considering that they propagate indevelopment in the nervous device to the central nervous device and also propagate regulates initiated in the central nervous device to the perimeter. Consequently, it is essential to understand thoabout their properties. To answer the concerns of just how action potentials are initiated and also propagated, we have to record the potential between the inside and outside of nerve cells making use of intracellular recording approaches.

1.3 Intracellular Recordings from Neurons


The potential distinction across a nerve cell membrane can be measured via a microelectrode whose pointer is so tiny (around a micron) that it deserve to penetrate the cell without producing any type of damages. When the electrode is in the bath (the extracellular medium) tright here is no potential tape-recorded bereason the bath is isopotential. If the microelectrode is carefully inserted right into the cell, there is a sharp adjust in potential. The analysis of the voltmeter instantaneously changes from 0 mV, to reading a potential difference of -60 mV inside the cell through respect to the outside. The potential that is videotaped when a living cell is impaled through a microelectrode is referred to as the resting potential, and varies from cell to cell. Here it is shown to be -60 mV, yet have the right to selection in between -80 mV and -40 mV, depending upon the particular kind of nerve cell. In the absence of any type of stimulation, the relaxing potential is mostly continuous.

It is additionally possible to document and research the activity potential. Figure 1.3 illustprices an example in which a neuron has currently been impaled via one microelectrode (the recording electrode), which is connected to a voltmeter. The electrode records a resting potential of -60 mV. The cell has likewise been impaled through a second electrode dubbed the stimulating electrode. This electrode is linked to a battery and a maker that have the right to monitor the amount of existing (I) that flows via the electrode. Changes in membrane potential are developed by closing the switch and also by systematically altering both the dimension and also polarity of the battery. If the negative pole of the battery is linked to the inside of the cell as in Figure 1.3A, an instantaneous readjust in the amount of existing will circulation through the stimulating electrode, and the membrane potential becomes transiently more negative. This result should not be surprising. The negative pole of the battery makes the inside of the cell even more negative than it was prior to. A readjust in potential that boosts the polarized state of a membrane is dubbed a hyperpolarization. The cell is even more polarized than it was usually. Use yet a larger battery and also the potential becomes also bigger. The resultant hyperpolarizations are graded features of the magnitude of the stimuli offered to develop them.


Now take into consideration the situation in which the positive pole of the battery is linked to the electrode (Figure 1.3B). When the positive pole of the battery is linked to the electrode, the potential of the cell becomes more positive as soon as the switch is closed (Figure 1.3B). Such potentials are dubbed depolarizations. The polarized state of the membrane is decreased. Larger batteries develop even larger depolarizations. Again, the magnitude of the responses are proportional to the magnitude of the stimuli. However, an unusual event occurs as soon as the magnitude of the depolarization reaches a level of membrane potential referred to as the threshold. A completely new type of signal is initiated; the action potential. Keep in mind that if the size of the battery is increased even more, the amplitude of the action potential is the same as the previous one (Figure 1.3B). The process of eliciting an action potential in a nerve cell is analogous to igniting a fusage via a warmth resource. A specific minimum temperature (threshold) is vital. Temperatures much less than the threshold fail to ignite the fuse. Temperatures greater than the threshost ignite the fusage just as well as the threshold temperature and the fusage does not burn any brighter or hotter.

If the suprathreshold present stimulus is long sufficient, yet, a train of activity potentials will be elicited. In basic, the activity potentials will continue to fire as lengthy as the stimulus proceeds, through the frequency of firing being proportional to the magnitude of the stimulus (Figure 1.4).


Action potentials are not only initiated in an all-or-nothing fashion, but they are also propagated in an all-or-nothing fashion. An activity potential initiated in the cell body of a motor neuron in the spinal cord will propagate in an undecremented fashion all the way to the synaptic terminals of that motor neuron. Aget, the situation is analogous to a burning fusage. Once the fuse is ignited, the flame will spreview to its finish.

1.4 Materials of the Action Potentials

The activity potential is composed of a number of components (Figure 1.3B). The threshold is the value of the membrane potential which, if got to, leads to the all-or-nothing initiation of an activity potential. The initial or increasing phase of the action potential is referred to as the depolarizing phase or the upstroke. The region of the activity potential in between the 0 mV level and the height amplitude is the overshoot. The rerevolve of the membrane potential to the resting potential is referred to as the repolarization phase. There is additionally a phase of the activity potential during which time the membrane potential deserve to be more negative than the relaxing potential. This phase of the action potential is referred to as the undershoot or the hyperpolarizing afterpotential. In Figure 1.4, the undershoots of the activity potentials perform not end up being even more negative than the relaxing potential bereason they are "riding" on the constant depolarizing stimulus.

1.5 Ionic Mechanisms of Resting Potentials

Before researching the ionic mechanisms of action potentials, it is first essential to understand also the ionic mechanisms of the resting potential. The 2 phenomena are intimately associated. The story of the relaxing potential goes ago to the at an early stage 1900"s when Julius Bernstein said that the relaxing potential (Vm) was equal to the potassium equilibrium potential (EK). Where

The key to understanding the relaxing potential is the reality that ions are dispersed unequally on the inside and also external of cells, and that cell membranes are selectively permeable to different ions. K+ is specifically essential for the relaxing potential. The membrane is very permeable to K+. In addition, the inside of the cell has a high concentration of K+ (i) and the exterior of the cell has a low concentration of K+ (o). Thus, K+ will certainly normally move by diffusion from its area of high concentration to its area of low concentration. Consequently, the positive K+ ions leaving the inner surchallenge of the membrane leave behind some negatively charged ions. That negative charge attracts the positive charge of the K+ ion that is leaving and also has a tendency to "pull it back". Therefore, tbelow will certainly be an electrical force directed inward that will certainly tfinish to counterbalance the diffusional force directed outside. Eventually, an equilibrium will be established; the concentration pressure moving K+ out will certainly balance the electrical pressure holding it in. The potential at which that balance is completed is referred to as the Nernst Equilibrium Potential.


An experiment to test Bernstein"s hypothesis that the membrane potential is equal to the Nernst Equilibrium Potential (i.e., Vm = EK) is shown to the left.

The K+ concentration exterior the cell was systematically varied while the membrane potential was measured. Also shown is the line that is predicted by the Nernst Equation. The experimentally measured points are extremely cshed to this line. Additionally, bereason of the logarithmic relationship in the Nernst equation, a readjust in concentration of K+ by a factor of 10 results in a 60 mV change in potential.

Keep in mind, but, that there are some deviations in the number at left from what is predicted by the Nernst equation. Thus, one cannot conclude that Vm = EK. Such deviations suggest that an additional ion is also involved in generating the resting potential. That ion is Na+. The high concentration of Na+ exterior the cell and reasonably low concentration inside the cell results in a chemical (diffusional) driving pressure for Na+ influx. Tbelow is also an electric driving pressure because the inside of the cell is negative and also this negativity attracts the positive sodium ions. Consequently, if the cell has a small permecapability to sodium, Na+ will relocate throughout the membrane and the membrane potential would certainly be even more depolarized than would be supposed from the K+ equilibrium potential.

1.6 Goldman-Hodgkin and also Katz (GHK) Equation

When a membrane is permeable to 2 different ions, the Nernst equation deserve to no longer be provided to precisely determine the membrane potential. It is possible, but, to apply the GHK equation. This equation describes the potential across a membrane that is permeable to both Na+ and also K+.

Note that α is the ratio of Na+ permecapacity (PNa) to K+ permeability (PK). Keep in mind also that if the permeability of the membrane to Na+ is 0, then alpha in the GHK is 0, and also the Goldman-Hodgkin-Katz equation reduces to the Nernst equilibrium potential for K+. If the permecapability of the membrane to Na+ is very high and also the potassium permeability is very low, the terms become very huge, dominating the equation compared to the terms, and the GHK equation reduces to the Nernst equilibrium potential for Na+.

If the GHK equation is applied to the exact same information in Figure 1.5, there is a far better fit. The value of alpha necessary to obtain this excellent fit was 0.01. This indicates that the potassium K+ permecapacity is 100 times the Na+ permecapability. In summary, the resting potential is due not just to the fact that tright here is a high permecapacity to K+. There is likewise a slight permeability to Na+, which often tends to make the membrane potential slightly even more positive than it would certainly have actually been if the membrane were permeable to K+ alone.


1.7 Membrane Potential Laboratory

Click here to go to the interenergetic Membrane Potential Laboratory to experiment with the results of changing external or interior potassium ion concentration and membrane permeability to sodium and also potassium ions. Predictions are made using the Nernst and the Goldmale, Hodgkin, Katz equations.

Membrane Potential Laboratory

 

Test Your Knowledge

 


If a nerve membrane suddenly came to be equally permeable to both Na+ and also K+, the membrane potential would:

A. Not change

B. Approach the new K+ equilibrium potential

C. Approach the new Na+ equilibrium potential

D. Approach a worth of about 0 mV

E. Approach a continuous worth of about +55 mV


If a nerve membrane all of a sudden became equally permeable to both Na+ and K+, the membrane potential would:

A. Not readjust This answer is INCORRECT.

A adjust in permecapacity would certainly depolarize the membrane potential considering that alpha in the GHK equation would certainly equal one. Initially, alpha was 0.01. Try substituting different worths of alpha into the GHK equation and calculate the resultant membrane potential.

B. Approach the brand-new K+ equilibrium potential

C. Approach the brand-new Na+ equilibrium potential

D. Approach a worth of around 0 mV

E. Approach a constant worth of around +55 mV


If a nerve membrane suddenly ended up being equally permeable to both Na+ and K+, the membrane potential would:

A. Not readjust

B. Approach the brand-new K+ equilibrium potential This answer is INCORRECT. The membrane potential would certainly method the K+ equilibrium potential only if the Na+ permecapacity was decreased or the K+ permecapacity was boosted. Also tbelow would be no "new" equilibrium potential. Changing the permecapability does not readjust the equilibrium potential.

C. Approach the brand-new Na+ equilibrium potential

D. Approach a worth of about 0 mV

E. Approach a continuous value of around +55 mV


If a nerve membrane unexpectedly became equally permeable to both Na+ and also K+, the membrane potential would:

A. Not adjust

B. Approach the brand-new K+ equilibrium potential

C. Approach the new Na+ equilibrium potential This answer is INCORRECT. The membrane potential would technique the Na+ equilibrium potential only if alpha in the GHK equation came to be very huge (e.g., decrease PK or increase PNa). Also, tright here would certainly be no "new" Na+ equilibrium potential. Changing the permecapacity does not change the equilibrium potential; it changes the membrane potential.

D. Approach a worth of about 0 mV

E. Approach a constant value of about +55 mV


If a nerve membrane all of a sudden came to be equally permeable to both Na+ and K+, the membrane potential would:

A. Not readjust

B. Approach the brand-new K+ equilibrium potential

C. Approach the brand-new Na+ equilibrium potential

D. Approach a worth of about 0 mV This answer is CORRECT! Roughly speaking, the membrane potential would relocate to a worth half method between EK and ENa. The GHK equation could be supplied to determine the precise worth.

E. Approach a continuous worth of around +55 mV


If a nerve membrane suddenly ended up being equally permeable to both Na+ and K+, the membrane potential would:

A. Not readjust

B. Approach the new K+ equilibrium potential

C. Approach the new Na+ equilibrium potential

D. Approach a value of about 0 mV

E. Approach a consistent value of around +55 mV This answer is INCORRECT. The membrane potential would certainly not strategy a worth of around +55 mV (the approximate value of ENa) unmuch less tbelow was a big rise in the sodium permeability without a matching readjust in the potassium permeability. Alpha in the Goldman equation would must method a very high worth.


If the concentration of K+ in the cytoplasm of an invertebrate axon is readjusted to a new worth of 200 mM (Note: for this axon normal o = 20 mM and normal i = 400 mM): 

A. The membrane potential would certainly end up being more negative This answer is INCORRECT. The normal value of extracellular potassium is 20 mM and the normal value of intracellular potassium is 400 mM, yielding a normal equilibrium potential for potassium of around -75 mV. If the intracellular concentration is adjusted from 400 mM to 200 mM, then the potassium equilibrium potential as established by the Nernst equation, will certainly equal around -60 mV. Because the membrane potential is generally -60 mV and also is dependent, to a huge extent, on EK, the change in the potassium concentration and therefore EK would certainly make the membrane potential more positive, not more negative.

B. The K+ equilibrium potential would adjust by 60 mV

C. The K+ equilibrium potential would certainly be about -60 mV

D. The K+ equilibrium potential would be about -18 mV

E. An action potential would be initiated


If the concentration of K+ in the cytoplasm of an invertebrate axon is changed to a new value of 200 mM (Note: for this axon normal o = 20 mM and normal i = 400 mM): 

A. The membrane potential would end up being more negative

B. The K+ equilibrium potential would change by 60 mV This answer is INCORRECT. The potassium equilibrium potential would not change by 60 mV. The potassium concentration was adjusted simply from 400 mM to 200 mM. One have the right to usage the Nernst equation to determine the specific worth that the equilibrium potential would readjust by. It was initially about -75 mV and also as a result of the readjust in concentration, the equilibrium potential becomes -60 mV. Thus, the equilibrium potential does not adjust by 60 mV, it transforms by about 15 mV.

C. The K+ equilibrium potential would certainly be about -60 mV

D. The K+ equilibrium potential would be about -18 mV

E. An action potential would certainly be initiated


If the concentration of K+ in the cytoplasm of an invertebprice axon is readjusted to a brand-new worth of 200 mM (Note: for this axon normal o = 20 mM and also normal i = 400 mM): 

A. The membrane potential would certainly come to be even more negative

B. The K+ equilibrium potential would adjust by 60 mV

C. The K+ equilibrium potential would be about -60 mV This answer is CORRECT! This is the correct answer. See the logic defined in responses A and also B.

D. The K+ equilibrium potential would be about -18 mV

E. An action potential would be initiated


If the concentration of K+ in the cytoplasm of an invertebprice axon is changed to a brand-new worth of 200 mM (Note: for this axon normal o = 20 mM and also normal i = 400 mM): 

A. The membrane potential would certainly become even more negative

B. The K+ equilibrium potential would certainly adjust by 60 mV

C. The K+ equilibrium potential would certainly be around -60 mV

D. The K+ equilibrium potential would certainly be around -18 mV This answer is INCORRECT.

See more: Why Is Phenol Much More Acidic Than Cyclohexanol ? Phenol Is More Acidic Than Cyclohexanol

Using the Nernst equation, the new potassium equilibrium potential have the right to be calculated to be -60 mV. A value of -18 mV would be calculated if you substituted o = 200 and i= 400 into the Nernst equation.

E. An action potential would be initiated


If the concentration of K+ in the cytoplasm of an invertebrate axon is changed to a brand-new value of 200 mM (Note: for this axon normal o = 20 mM and also normal i = 400 mM): 

A. The membrane potential would become even more negative

B. The K+ equilibrium potential would certainly readjust by 60 mV

C. The K+ equilibrium potential would certainly be about -60 mV

D. The K+ equilibrium potential would be about -18 mV

E. An activity potential would certainly be initiated This answer is INCORRECT. The membrane potential would not depolarize sufficiently to reach threshost (around -45 mV).