Electrical Activity of Nerve Cells


Electrical Activity of Nerve Cells

The transmission of information from one nerve cell to another in the nervous system is by the generation of electrical impulses.  In some ways this is similar to a computer which transmits information in the form of pulses of electrical voltage that encode bits of information as a 0 or 1. There are some fundamental differences, however, in that the digital voltage changes used in computers are generated by the movement of electrons, while the voltage changes in nerve cells are created by the movement of ions such as a sodium ion (Na+)  and a potassium ion (K+).  In addition, the movement of electrons is transmitted along the length of wires, while the movement of ions occur across cell membranes and then along the length of nerve fibers.  The movement of ions across cell membranes is through so-called ion channels.   These channels are highly regulated and specific for certain types of ions.

Ion Channels in Nerve Cell Membranes 





 Types of ion channels (a) Passive membrane channels are always open. (b) Chemically activated ion channels are opened with binding of neurotransmitter. (C) Voltage-gated ion channels are opened with change in membrane potential.

The electrical impulse used by nerve cells for the transmission of information is called an action potential and is dependent on the properties of the axon membrane.  As are all cell membranes, this membrane is made up of a double layer of lipids, with specialized proteins penetrating the double layer.  These proteins regulate the movement of ions across the membrane, which in turn creates the action potential. Certain ions (Na+, K+, Cl-, and Ca2+) can cross the membrane only through protein pores in the membrane that form the ion channels.  These channels typically allow only specific ions to pass, while blocking others because of their size, charge, or state of hydration.  There are three basic types of ion channels: passive, chemically activated, and voltage-activated channels.

Passive ion channels are found in membranes throughout all areas of the nerve cell.  Each passive channel is identified according to the specific ion it allows through (e.g., Na+ channel, K+ channel, Cl- channel, and Ca2+ channels).

Chemically activated ion channels are located predominantly on dendrites and the soma.  These channels are generally closed by "gates" to prevent the flow of ions through the membrane.  Chemical transmitters bind to sites on these protein channels and open the gate across the channel to permit the flow of ions through the channel.  These chemically activated channels are also known as receptors.

Voltage-activated ion channels, found in the membranes of axons and soma, are opened when they detect a certain voltage. They are responsible for generating and propagating the action potential.



The Membrane Potential and the Action Potential 



 
The movement of ions across their channels is caused by a difference in the electrical charge or differences in the concentration of ions between one side of the membrane and the other.  The imbalance in ionic concentration is called the concentration gradient.  The resulting imbalance in electrical charge is called the membrane potential.

Resting cells, cells not in the process of conducting nervous impulses, have a stable membrane potential.  The onset of an action potential, in which the membrane potential temporarily changes, indicates a cell in the process of nervous conduction.

The membrane potential exists because of a difference in the number of positive and negative charges across the membrane. These charges are attributed to the cations (positively charged ions) and anions (negatively charged ions) that occur on each side of the membrane. When there is a difference in the net charge between the inside and outside of a cell, an electrical potential (E) is established. This electrical potential is measured in units called volts (V) and is determined by the charge difference between two points. The charge at two points in the extracellular fluid is the same, for example, so the charge difference and electrical potential are therefore zero. In contrast, since there is a charge difference between a point in the extracellular space and a point within the cell, an electrical potential is established. In many nerve cells, this electrical potential difference across the membrane, Em, is approximately -0.060 V or -60 mV. The convention that has been adopted for measuring the voltage differences across the membrane is to use the extracellular voltage as a reference. A minus sign thus indicates that the inside of the cell is more negative than the extracellular fluid.

The electrical potential can be viewed as the electrical equivalent to pressure. Differences in wind pressure between two points cause currents of air molecules to flow. In a similar fashion, an electrical potential results in the movement of ions or electrons.  In physical systems, the movement of electrons in a copper wire is the basis of current flow. In biological systems, current flow is due to the movement of ions.  This movement occurs when anions are attracted to positively charged regions and cations to negatively charged regions.  The flow of ions is called ionic current (I)  and is measured in units called amperes (A).  The ionic sodium current, INa+, that moves through a single channel, for example, is approximately 12 x 10-12 A.

The ease with which ions can flow through an ion channel is called conductance (G) and is measured in dimensional units called siemens (S). Several factors affect the conductance of an ion through a channel. The first is the size of the ion relative to that of the channel. If the channel is large in comparison to the size of the ion, the ion will pass with relative ease and the channel therefore has a high conductance. A smaller channel increases the probability of the ion colliding with the walls of the channel, making it more difficult for the ion to pass. Smaller channels therefore have a lower conductance. Other factors, such as the charge of an ion and its state of hydration (the addition of water molecules), can also affect its conductance through the channel. Each type of channel has a specific conductance for its associated ion. Sodium ion channels, for example, have a conductance of 15 x 10-12 S, while calcium ion channels have a conductance of 1 x 10-12 S. Consequently, a sodium ion is able to move through its channel more easily than calcium ions can move through a calcium channel.

The relationship between electrical potential, ionic current, and conductance is given by Ohm's Law. This law states that the rate of ion flow through a channel is directly proportional to the conductance of the channel and the magnitude of the electrical potential, I=G x E. Larger electrical potentials and greater channel conductances produce a faster flow of ions across the membrane. This is similar to the flow of water through a tube. Larger pressures and tubes with bigger diameters will allow more water to flow.


 
The overall effect of all of the channels for a particular ion is called the membrane conductance for that ion. Membrane conductance of an ion, therefore, depends on the number or density of a particular type of channel within a region of the membrane. Membrane conductance can vary from one region of a nerve cell to another. The membrane conductance for sodium ions, for instance, is greater in the region of the axon hillock or initial segment of the axon, and nodes of Ranvier than in other areas of the cell. As we will learn, this regional difference in the number of Na+ channels aids in the initiation and propagation of the action potential, the basis of nervous impulses.


Ion Concentration Gradients and Diffusion  

 

The distribution of ions in the extra- and intracellular spaces of nerve cells is similar to that of most cells in the body.  The inside of nerve cells has a relatively high concentration of K+ ions and a low concentration of Na+. In contrast, the extracellular fluid contains a relatively low concentration of K+ ions and a high concentration of Na+.  The high intracellular concentration of K+ ions in comparison to the extracellular compartment produces a concentration gradient that causes K+ to diffuse out of the nerve cell through the passive K+ channels.  Similarly, the high extracellular concentration of Na+ causes Na+ to diffuse into the cell through passive Na+ channels.  If the diffusion of these ions continued, the concentration gradients would eventually equilibrate, and the intracellular concentrations of K+ and Na+ would be equal to their respective extracellular concentrations.  The action of the Na/K-ATPase pumping mechanisms, however, works to transport Na+ ions back out to the extracellular compartment and K+ back into the intracellular compartment.  Consequently, the Na/K pumping mechanisms maintains the Na+ and K+ gradients despite the continued diffusion of the ions across the membrane.

Differences Between the Membrane Potential and the Equilibrium Potential - A Driving Force for Ion Movement 
 


To understand how the membrane potential is established, let us first consider a hypothetical cell that contains only K+ ions and large negatively charged organic anions, represented as A-.  These anions are charged amino acids and proteins that are too large to pass through the ion channels of the membrane.  Assume that inside a nerve cell are relatively high concentrations of K+ and A- ions, and that initially these ions do not exist in the extracellular fluid.  As we discussed earlier, the establishment of concentration gradients would cause K+ and A- to diffuse out of the cell through passive channels. In our hypothetical cell, however, only K+ ions can diffuse across the membrane.  If K+ and A- are initially contained within the cell in equal concentrations, then before diffusion starts there will be no net charge (Panel a). As K+ begins to diffuse outward, fewer K+ ions are available inside the cell to balance the negatively charged A- ions.  Consequently, the interior of the cell becomes more negative than the outside of the cell (Panel b).  As we learned earlier, when the cytosol and the extracellular fluid have different numbers of charged ions, an electrical potential develops and the charged ions are attracted to the region that is oppositely charged.  The electrical force established by the negatively charged interior of the cell attracts positive ions, causing them to flow from the extracellular fluid across the membrane to the cytosol.  Therefore, even though the concentration gradient for K+ alone would continue to force K+ ions outward, an electrical force gradually develops, attracting K+ ions back into the cell (Panel c).  As more and more K+ ions leave the cell, a greater electrical force develops.  Eventually, because of the opposing concentration gradient (Panel d), the electrical force becomes sufficient to draw K+ ions into the cell at the same rate that they leave the cell.  The voltage at this particular electrical force is known as the equilibrium potential or reversal potential.  The equilibrium potential for any ion is the potential at which the efflux and influx of an ion are the same so that the net flux across the membrane for that ion is zero.     The equilibrium potential can be expressed as the product of several constants and the logarithm of the ratio of the extra- and intracellular concentration of a particular ion, and can be described by the Nernst equation.

Eion= RT  x  loge  [ion]o

         zF               [ion]i


where R is the gas constant, T is the absolute temperature, z is the ion valance, and F is the Faraday constant.  At 20°C this expression for K+ is reduced to

EK=  58 x log10  [K+]o

                        [K+]i                     

Typically the ratio of [K+]o/[K+]i results in a value of EK of about -75 mV.

Thus, for this simple cell that contains only K+ and A- and allows only K+ to cross the membrane, the membrane potential is equal to the equilibrium potential of K+.  Nerve cells in general, however, contain other ions that affect the membrane potential of the cell.  The two other major ions that contribute to the membrane potential are Na+ and Cl-.  Both Na+ and Cl- have very high extracellular concentrations in comparison to their intracellular concentrations and therefore passively diffuse into the cell. Na+ and Cl- do not diffuse across the cell membrane as easily as K+ ions.  When the nerve cell is at "rest"-that is, when it does not generate an action potential-its membrane is most permeable to K+.  This is the reason that the resting membrane potential is near the equilibrium potential for K+.  (Typically, the K+ equilibrium potential, EK+, is approximately -75 mV; the resting membrane potential, Em, is -60 mV; and the Na+ equilibrium potential, ENa+, is +55 mV.)  The factors that affect the resting membrane potential, Em, can be expressed in terms of the intra- and extracellular concentrations of Na+, K+, and Cl- ions, as well as their membrane permeabilities, PNa, PK, and PCl. This relation is given by the Goldman equation.

Em = RT  x  ln  Pk [K+]o  + PNa  [Na+]o  +  PCl [Cl-]i

         zF          Pk [K+]i  + PNa  [Na+]i  +  PCl [Cl-]o

We will learn later that during the action potential, there are changes in the relative permeabilities of K+ and Na+ that account for changes in the membrane potential.

The Action Potential - A Temporary Change in the Membrane Potential 


 

Action potentials are electrical impulses
transmitted by nerve cells. They can be thought of as a change in the voltage of the membrane potential that causes it to go from its negative resting state to a positive value for a very brief time. This type of change in the membrane potential is typically found in nerve axons.  The figure shows the changes in the membrane potential that characterize the action potential.  The membrane potential is initially at its resting level of -60 mV.  As the membrane potential becomes more positive (a process called
depolarization), it reaches a threshold value at approximately - 45 mV.  After reaching threshold, the membrane potential rapidly changes to more positive values during a rising phase.  It reaches a peak at +25 mV and begins to repolarize.  In repolarization, the membrane becomes hyperpolarized, or more negative than in the original resting state. It remains hyperpolarized for a time before returning to the resting level of -60 mV.

What causes such a drastic change in the membrane potential? The voltage changes seen in the action potential are a result of the opening and closing of voltage-sensitive ion channels that control the influx of Na+ and efflux of K+.  These channels are sensitive to the voltage across the membrane.  When they detect that the voltage has reached a threshold level, they open their gates to allow the passage of these ions.  The sodium channel appears to have three states of operation, a resting state, an activating state, and an inactivating state.  When the nerve cell is at rest, the sodium channel is in its resting state, and its gates are closed to prevent the influx of Na+ ions.  If the nerve cell is stimulated and the membrane potential is depolarized to the threshold value of approximately -45 mV, the sodium channel switches from its resting state to the activating or open state.  Sodium ions flow into the cell until the inactivating gate closes the channel.  The closing of the inactivating gate is a time-dependent phenomenon and is independent of the opening of the activation gate.  Thus, Na+ channel activation and inactivation can be thought of as two separate gates that open and close independently.  The inactivating gate remains closed for a period of time, after which both gates return to their resting state.  The properties of the sodium channel, therefore, are dependent on voltage and time.  Once the threshold value of voltage is reached, it triggers this series of events that is carried out sequentially.

 


 
A threshold value of voltage also opens voltage-sensitive K+ channels, but the process is entirely different from the opening of Na+ channels Unlike the Na+ channel, there is no inactivation gate in the K+ channel.  Also, the K+ channels open more slowly than the Na+ channels and remain open until they sense a particular voltage.  The closing of these channels is not a time-dependent process; it depends only on the voltage, the membrane potential. When the membrane is depolarized, the K+ channels remain in the open state; when the membrane potential repolarizes, the K+ channels close.


Action Potential Ion Channels 
 

The influx of Na+ ions and efflux of K+ ions produce the action potential.  In the resting state, voltage-sensitive Na+ and K+ ion channels are closed.  The simultaneous activation of many sodium channels in the membrane of an axon causes an influx of Na+ ions.  This influx of positive charges causes the membrane potential to become more positive, producing a gradual depolarization of the membrane.  Once the threshold value of the membrane potential has been reached (typically -45 mV at the initial segment), a series of events is triggered, leading to the initiation or generation of the action potential.  At the threshold level of the membrane potential, more voltage-sensitive sodium channels are activated, resulting in a greater influx of Na+ ions.  This influx of positive charges depolarizes the membrane still further, leading to a further influx of Na+ and consequently a further depolarization.

 

This regenerative process is the basis for the rising phase of the action potential once threshold has been reached.  The regenerative process can occur at different speeds depending on how much the membrane is depolarized and how quickly the membrane potential achieves the threshold value.  Greater depolarizations of the membrane potential above the threshold can lead to the opening of more sodium channels, in turn depolarizing the membrane even faster.
Note that not all depolarizations will result in an action potential.  If the depolarization is too small, too few voltage-sensitive sodium channels will be activated to perpetuate the regenerative process and no action potential will be produced.  Thus, the action potential is an "all-or-none" phenomenon.

At the peak of the action potential the membrane is much more permeable to Na+ than to K+; consequently, the value of the membrane potential is closer to the Na+ equilibrium potential than to the K+ equilibrium potential.  After the peak has been reached the inactivation channels close, Na+ influx is blocked, and the membrane potential begins to repolarize.  The membrane potential repolarizes because at this point the membrane conductance for K+ is greater than that for Na+.  As the sodium channels begin to become inactivated, the potassium channels begin to become activated.  This increase in potassium conductance causes the membrane potential to become more negative and contributes to the repolarization phase of the action potential.  Finally, the prolonged opening of K+ channels causes a continued efflux of K+ ions.  This removal of positive charges from the cell in turn causes the membrane potential to remain hyperpolarized briefly before returning to the resting level.


Action Potential Refractory Periods 

 
For a period of time just after the initiation of an action potential, the axon is unable to generate a second action potential regardless of how much the membrane is depolarized.  This phase is known as the absolute refractory period and typically lasts several milliseconds after the onset of the first action potential (Fig. 7-19).  After this period, an axon is capable of initiating a second action potential, but only if the membrane is depolarized to a large degree.  During this relative refractory period, the threshold voltage needed to initiate an action potential becomes much greater.

What causes this increase in threshold? In the absolute refractory period, the Na+ inactivation gates are still in their closed state and have not been reset. Consequently, no matter what the voltage difference across a sodium channel, the channel will not open. In the relative refractory period, many (but not all) of the sodium channels have now been reset. Thus a greater depolarization is needed to trigger the regenerative process required to initiate the second action potential. The significance of the absolute refractory period is that its time interval determines the fastest frequency at which an axon can generate action potentials.

Action Potential Propagation 


Thus far we have considered how an action potential is initiated. After initiation it propagates, or moves, along the axon from the region of the initial segment down to the terminal endings. How does this propagation occur?

Let us first consider the axon as a tube with many membrane regions. In its resting (nonconducting) state, concentrations of various ions are maintained by various active transport systems. Assume that the first membrane region generates an action potential so that Na+ ions flow into the axon at this point. The sodium ions come from the extracellular fluid surrounding adjacent membrane regions. The removal of Na+ ions from adjacent regions causes these regions to depolarize. Since current flow follows the path of a loop, the influx of Na+ ions in the region of the action potential is followed by the movement of positive charges into the adjacent areas of the membrane. The depolarization of adjacent membrane regions is therefore aided by the movement of positively charged ions within the nerve fiber along its length. If this depolarization is sufficient to reach threshold, it will initiate an action potential in the second region. In this manner, each successive region is depolarized to threshold and generates an action potential. As a consequence of these mechanisms, the action potential propagates in a direction from the soma to the axon terminal.


 

Propagation Velocity of the Action Potential 

The propagation of an action potential along the axon occurs at a constant speed.  In unmyelinated nerve fibers, the conduction velocity is proportional to the diameter of the axon. The larger the diameter of the axon, the greater the speed of propagation.  This is because axons with large diameters do not offer as much resistance to the flow of ions along the length of the axon.  In myelinated axons, the velocity of propagation is determined not only by the diameter of the axon but also by the distance between the nodes of Ranvier.


 

The formation of myelin around an axon prevents the penetration of ions needed for the conduction of the action potential. Between the segments of myelin, however, are nodes of Ranvier, where the membrane of the nerve axon is exposed and contains large numbers of Na+ channels.  It is in the nodes of Ranvier that the membrane is depolarized and action potentials are generated.  The generation of an action potential in one node of Ranvier causes the membrane potential in the adjacent node of Ranvier to depolarize and also to generate an action potential.  In this way, the propagation of an action potential along a myelinated nerve axon appears to jump (saltus in Latin) from one node of Ranvier to the next in the process of saltatory conduction.  Thus the greater the distance between nodes of Ranvier, the greater the velocity of action potential propagation.

When the action potential reaches the end of the axon, it invades the synaptic terminal.  This structure is one of the key elements in the communication between nerve cells.  At the synaptic terminal, the action potentials transmitted along the axon cause the release of chemicals used in the communication between neurons in a process called synaptic transmission.

External Links to Related Topics

Video – action potential simulation

                                                                                                       
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