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Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000.

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Molecular Cell Biology. 4th edition.

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Section 21.2The Action Potential and Conduction of Electric Impulses

We saw in Chapter 15 that a voltage gradient, also called an electric potential, exists across the plasma membrane of all cells. The potential across the plasma membrane of large cells can be measured with a microelectrode inserted inside the cell and a reference electrode placed in the extracellular fluid. The two are connected to a voltmeter capable of measuring small potential differences (Figure 21-7). In virtually all cases the inside of the cell membrane is negative relative to the outside; typical membrane potentials are between −30 and −70 mV. The potential across the surface membrane of most animal cells generally does not vary with time. In contrast, neurons and muscle cells — the principal types of electrically active cells — undergo controlled changes in their membrane potential (see Figure 21-2a).

Figure 21-7. Measurement of the electric potential across an axonal membrane.

Figure 21-7

Measurement of the electric potential across an axonal membrane. A microelectrode, constructed by filling a glass tube of extremely small diameter with a conducting fluid such as KCl, is inserted into an axon in such a way that the surface membrane seals (more...)

The characteristic electrical activity of neurons — their ability to conduct, transmit, and receive electric signals — results from the opening and closing of specific ion-channel proteins in the neuron plasma membrane (Figure 21-8). Each open channel allows only a small number of ions to move from one side of the membrane to the other, yet these ion movements cause significant changes in the membrane potential. Here we explain the relationship between opening and closing of ion channels and the resultant changes in the voltage across the membrane that lead to propagation of action potentials. We examine the structure and operation of several types of ion channels critical to neuron functioning in more detail later in the chapter.

Figure 21-8. Ion channels in neuronal plasma membranes.

Figure 21-8

Ion channels in neuronal plasma membranes. Each type of channel protein has a specific function in the electrical activity of neurons. (a) Resting K+ channels are responsible for generating the resting potential across the membrane. (b) Voltage- gated (more...)

The Resting Potential, Generated Mainly by Open “Resting” K+ Channels, Is Near EK

The concentration of K+ ions inside typical metazoan cells is about 10 times that in the extracellular fluid, whereas the concentrations of Na+ and Cl ions are much higher outside the cell than inside; these concentration gradients are maintained by Na+/K+ ATPases with the expenditure of cellular energy (see Figure 15-13). As noted in Chapter 15, the plasma membrane contains abundant open “resting” K+ channels that allow passage only of K+. The resting potential — inside negative — is determined mainly by the movement of K+ ions: Movement of a K+ ion across the membrane down its concentration gradient leaves an excess negative charge on the cytosolic face and deposits a positive one on the exoplasmic face (Figure 21-9). Quantitatively, the usual resting potential of −60 mV is close to, but in magnitude less than, the value of EK, the potassium equilibrium potential, calculated from the Nernst equation (see Equation 15-7) and the typical external and cytosolic K+ concentrations ([Ko] and [Ki], respectively) given in Figure 21-9. If the concentration of K+ surrounding a resting cell is changed, the measured membrane potential assumes a new value, again close to the calculated value of EK; this is evidence that the resting potential is due mainly to movement of K+ through open K+ channels in the plasma membrane.

Figure 21-9. Origin of the resting potential in a typical vertebrate neuron.

Figure 21-9

Origin of the resting potential in a typical vertebrate neuron. The ionic compositions of the cytosol and of the surrounding extracellular fluid are different. A represents negatively charged proteins, which neutralize the excess positive charges (more...)

The situation in cells is complicated because there are some open Na+ and Cl channels in the plasma membranes of the resting cell. Cells, of course, contain other ions, such as HPO42−, SO42−, and Mg2+, but there are few channels that admit these ions. Furthermore, the membrane potential of electrically active cells such as neurons and muscle cells is affected mainly by opening and closing channels for K+, Na+, and Cl; thus these three ions are the only ones we need consider here. As we discuss later, Ca2+ channels are central to the release of neurotransmitters at synapses.

To calculate the membrane potential as a function of the concentrations of different ions, it is useful to define a permeability constant P for each ion. P is a measure of the ease with which an ion can cross a unit area (1 cm2) of membrane driven by a 1 M difference in concentration; it is proportional to the number of open ion channels and to the number of ions each channel can conduct per second (the channel conductivity). Thus PK, PNa, and PCl are measures of the “leakiness” of a unit area of membrane to these ions. Permeabilities are generally not measured directly; rather, the permeability of a membrane for a given ion is the product of the number of open ion channels and the conductivity of each channel; both parameters can be measured by techniques we describe later. Since the conductivities of the various ion channels are nearly the same, differences in permeability of a membrane for Na+, K+, and Cl largely reflect differences in the number of open channels specific for each ion.

What is important is not the absolute magnitude of the permeabilities for each ion, but the ratios of the permeabilities of Na+ and Cl to that of K+. The electric potential, E (in millivolts), across a cell-surface membrane is given by a more complex version of the Nernst equation in which the concentrations of the ions are weighted in proportion to the relative magnitudes of their permeability constants:

Image ch21e1.jpg

where the “o” and “i” subscripts denote the ion concentrations outside and inside the cell. Because of their opposite charges (Z value in the Nernst equation), [Ko] and [Nao] are placed in the numerator, but [Clo] is placed in the denominator; conversely, [Ki] and [Nai] are in the denominator, but [Cli] is in the numerator. The membrane potential at any time and at any position in the neuron can be calculated with this equation if the relevant ion concentrations and permeabilities are known.

Note that if PNa = PCl = 0, then the membrane is permeable only to K+ ions and Equation 21-1 reduces to the Nernst equation for K+ (see Equation 15-7). Similarly, if PK = PCl = 0, then the membrane is permeable only to Na+ ions and Equation 21-1 reduces to the Nernst equation for Na+ (see Equation 15-6).

In resting neurons the ion concentrations are typically those shown in Figure 21-9, and the permeability of the membrane to Na+ or Cl ions is about one tenth that for K+ (i.e., PNa/PK = PCl/PK = 0.1). That is, there are about ten times more open K+ channels than open channels for Na+ or Cl. By substituting the typical ion concentrations and these permeability ratios into Equation 21-1, we can calculate the membrane potential as −52.9 mV, which is much closer to EK (−91.1 mV) than to ENa (+64.7 mV). Although ECl (−87.2 mV) is close to EK, there are so few open Cl channels that they contribute little to the resting potential. The resting potential is not equal to EK because the membrane also contains some open Na+ channels; influx of Na+ ions down its concentration gradient adds positive charges to the inside of the cell membrane, making the membrane potential more positive (or less negative).

Opening and Closing of Ion Channels Cause Predictable Changes in the Membrane Potential

It is clear from Equation 21-1 that changes in the permeability of the membrane to various ions will cause the membrane potential to change. Figure 21-10 illustrates several quantitative changes. Here we summarize the direction of the predicted changes due to opening and closing of various channels:

1.

Opening of Na+ channels (increasing PNa) causes depolarization of the membrane; the membrane potential becomes less negative, and if the increase in PNa is large enough, the potential can become positive inside, approaching ENa. Intuitively, Na+ ions tend to flow inward from the extracellular medium, down their concentration gradient, leaving excess negative ions on the outer surface of the membrane and putting more positive ions on the cytosolic surface. Conversely, closing of Na+ channels, decreasing PNa, causes membrane hyperpolarization, a more negative potential.

2.

Opening of K+ channels (increasing PK) causes hyperpolarization of the membrane; the membrane potential becomes more negative, approaching EK. Intuitively, this occurs because more K+ ions flow outward from the cytosol, down their concentration gradient, leaving excess negative ions on the cytosolic surface of the membrane and putting more positive ones on the outer surface. Conversely, closing of K+ channels, decreasing PK, causes depolarization of the membrane and a less negative potential.

3.

Opening of “nonspecific” cation channels that admit Na+ and K+ equally also causes membrane depolarization. Such channels allow K+ ions to flow outward from the cytosol and Na+ ions to flow inward; the net effect is to drive the membrane potential toward zero.

4.

Opening of Cl channels (increasing PCl) causes hyperpolarization of the membrane, and the potential approaches ECl. Intuitively, Cl ions tend to flow inward from the extracellular medium, down their concentration gradient, leaving excess positive ions on the outer surface of the membrane and putting more negative ions on the cytosolic surface. In muscle cells, resting Cl channels, not resting K+ channels, are the principal determinants of the inside negative resting potential. Conversely, closing of Cl channels, decreasing PCl, causes depolarization and a less negative potential.

At the resting potential, voltage-gated ion channels are closed; no ions move through them. However, when a region of the plasma membrane is depolarized slightly, voltage- gated Na+ channels open for a short period, allowing the influx of Na+ ions that causes the sudden and transient depolarization associated with an action potential. Following the opening (and closing) of voltage-gated Na+ channels during an action potential, the transient opening of voltage-gated K+ channels causes the membrane potential to return to the resting state and even become more negative (hyperpolarized) for a short time (see Figure 21-2a). The ability of axons to conduct action potentials over long distances without diminution thus depends on controlled opening and closing of voltage-gated Na+ and K+ channels (see Figure 21-8b). Binding of neurotransmitters to ligand-gated ion channels in postsynaptic cells triggers changes in the postsynaptic membrane potential during impulse transmission at synapses (see Figure 21-8c).

Figure 21-10. Effect of changes in ion permeability on membrane potential calculated with equation 21-1 using the permeability constants given in the text and the ion concentrations shown in Figure 21-9.

Figure 21-10

Effect of changes in ion permeability on membrane potential calculated with equation 21-1 using the permeability constants given in the text and the ion concentrations shown in Figure 21-9. The resting membrane potential is −53 mV; ENa, EK, and (more...)

Membrane Depolarizations Spread Passively Only Short Distances

To understand how voltage-gated Na+ and K+ channels allow an action potential to be conducted down an axon in one direction, we first need to examine how a plasma membrane with only resting K+ channels would conduct an electric depolarization. In its electric properties, a nerve cell with only resting K+ channels resembles a long underwater telephone cable. It consists of an electrical insulator, the poorly conducting cell membrane, separating two media — the cell cytosol and the extracellular fluid — that have a high conductivity for ions.

Suppose that a single microelectrode is inserted into the axon and that the electrode is connected to a source of electric current (e.g., a battery) such that the electric potential at that point is suddenly depolarized and maintained at this new voltage. At this site the inside of the membrane will have a relative excess of positive charges, principally K+ ions. These ions will tend to move away from the initial depolarization site, thus depolarizing adjacent sections of the membrane. This is called the passive spread of depolarization. In contrast to an action potential, passive spread occurs equally in both directions. Also, the magnitude of the depolarization diminishes with distance from the site of initial depolarization, as some of the excess cations leak back across the membrane through resting cation channels (Figure 21-11). Only a small portion of the excess cations are carried longitudinally along the axon for long distances. The extent of this passive spread of depolarization is a function of two properties of the nerve cells: the permeability of the membrane to ions and the conductivity of the cytosol.

Figure 21-11. Passive spread of a depolarization of a neuronal plasma membrane with only resting K+ ion channels.

Figure 21-11

Passive spread of a depolarization of a neuronal plasma membrane with only resting K+ ion channels. The neuronal membrane is depolarized from −70 to −40 mV at a single point and clamped at this value. The voltage is then measured at various (more...)

The passive spread of a depolarization is greater for large-diameter neurons than for small-diameter neurons, because the conductivity of the cytosol of a nerve cell depends on its cross-sectional area. The larger the area, the greater the number of ions there will be (per unit length of neuron) to conduct current. Thus K+ ions are able to move, on the average, farther along a large axon than a small one before they “leak” back across the membrane. As a consequence, large-diameter neurons passively conduct a depolarization faster and farther than thin ones. Nonetheless, a membrane depolarization can spread passively for only a short distance, from 0.1 to about 5 mm. Depolarizations in dendrites and the cell body generally spread in this manner, though some dendrites conduct an action potential. Neurons with very short axons also conduct axonal depolarizations by passive spread. However, passive spread does not allow propagation of electric signals over long distances.

As we discuss below, some axons are surrounded by a myelin sheath, which impedes the leakage of excess cations associated with membrane depolarization. Thus small myelinated neurons and large unmyelinated ones have similar length constants for passive spread of membrane depolarizations.

Voltage-Gated Cation Channels Generate Action Potentials

The action potential is a cycle of membrane depolarization, hyperpolarization, and return to the resting value (Figure 21-12a). The cycle lasts 1 – 2 ms, and can occur hundreds of times a second. These cyclical changes in the membrane potential result from transient increases in the permeability of a region of the membrane, first to Na+ ions, then to K+ ions (Figure 21-12b). More specifically, these electric changes are due to voltage-gated Na+ and K+ channels that open and shut in response to changes in the membrane potential. The role of these channels in the generation and conduction of action potentials was elucidated in classic studies done on the giant axon of the squid, in which multiple microelectrodes can be inserted without causing damage to the integrity of the plasma membrane. However, the same basic mechanism is used by all neurons.

Figure 21-12. Kinetics of changes in membrane potential and ion permeabilities during an action potential in the giant axon of a squid.

Figure 21-12

Kinetics of changes in membrane potential and ion permeabilities during an action potential in the giant axon of a squid. (a) Following stimulation at time 0, the membrane potential rapidly becomes more positive, approaching the value of ENa, and then (more...)

Voltage-Gated Na+ Channels

The sudden but short-lived depolarization of a region of the plasma membrane during an action potential is caused by a sudden massive, but transient, influx of Na+ ions through opened voltage-gated Na+ channels in that region. At the resting membrane potential these voltage-gated channels are closed. The depolarization of the membrane changes the conformation of the channel proteins, opening the Na+-specific channels and allowing Na+ influx through them.

During conduction of an action potential, the passive spread of depolarization to the adjacent distal region of membrane slightly depolarizes the new region, causing opening of a few voltage-gated Na+ channels and an increase in Na+ influx. A combination of two forces acting in the same direction drives Na+ ions into the cell: the concentration gradient of Na+ ions, and the resting membrane potential — inside negative — which tends to attract Na+ ions into the cell. As more Na+ ions enter the cell, the inside of the cell membrane becomes more positive and thus the membrane becomes depolarized further. This depolarization causes the opening of more voltage-gated Na+ channels, setting into motion an explosive entry of Na+ ions that is completed within a fraction of a millisecond. For a fraction of a millisecond, at the peak of the action potential, the permeability of this region of the membrane to Na+ becomes vastly greater than that for K+ or Cl, and the membrane potential approaches ENa, the equilibrium potential for a membrane permeable only to Na+ ions (see Figure 21-12).

When the membrane potential almost reaches ENa, further net inward movement of Na+ ions ceases, since the concentration gradient of Na+ ions (outside>inside) is balanced by the membrane potential ENa (inside positive). The action potential is at its peak. The measured peak value of the action potential for the squid giant axon is 35 mV, which is close to the calculated value of ENa (55 mV) based on Na+ concentrations of 440 mM outside and 50 mM inside. The relationship between the magnitude of the action potential and the concentration of Na+ ions inside and outside the cell has been confirmed experimentally. For instance, if the concentration of Na+ ions in the solution bathing the squid axon is reduced to one-third of normal, the magnitude of the depolarization is reduced by 40 mV, nearly as predicted.

Like all channel proteins, voltage-gated Na+ channels contain an aqueous pore through which the ions flow. Entering the channel from the outside, one encounters first a wide vestibule, then a narrow pore that selects the type of ion allowed to pass. The pore leads into a large inner vestibule and, at the cytosolic end, a segment of the protein — the “gate” — that closes the pore in the resting state. As depicted in Figure 21-13, in the resting state voltage-gated Na+ channels are closed but capable of being opened if the membrane is depolarized. The greater the depolarization, the greater the chance that any one channel will open. Opening is triggered by movement of voltage-sensing α helices in response to the membrane depolarization, causing a small conformational change in the gate that opens the channel and allows ion flow. Once opened, the channels stay open about 1 ms, during which time about 6000 Na+ ions pass through them. Further Na+ influx is prevented by movement of the channel-inactivating segment into the channel opening. As long as the membrane remains depolarized, the channel is inactivated and cannot be reopened. As we discuss later, this refractory period of the Na+ channel is important in determining the unidirectionality of the action potential. A few milliseconds after the inside-negative resting potential is reestablished, the channels return to the closed resting state, once again “primed” for being opened by depolarization.

Figure 21-13. Structure and function of the voltage-gated Na+ channel.

Figure 21-13

Structure and function of the voltage-gated Na+ channel. (Left) Like all voltage-gated channels, it contains four transmembrane domains, each of which contributes to the central pore through which ions move. The critical components that control movement (more...)

Voltage-Gated K+ Channels

During the time that the voltage-gated Na+ channels are closing and fewer Na+ ions are entering the cell, voltage-gated K+ channel proteins open. This causes the observed increase in potassium ion permeability and an increased efflux of K+ from the cytosol that repolarizes the plasma membrane to its resting potential. Actually, for a brief instant the membrane becomes hyperpolarized, with the potential approaching EK, which is more negative than the resting potential (see Figure 21-12).

Opening of the voltage-gated K+ channels is induced by the membrane depolarization of the action potential. Unlike the voltage-gated Na+ channels, most types of voltage-gated K+ channels remain open as long as the membrane is depolarized, and close only when the membrane potential has returned to an inside-negative value. Because the voltage-gated K+ channels open a fraction of a millisecond or so after the initial depolarization, they are called delayed K+ channels. Eventually all voltage-gated K+ and Na+ channels close. The only open channels are the non-voltage-gated K+ channels that generate the inside-negative potential characteristic of the resting state; as a result, the membrane potential returns to its resting value.

Action Potentials Are Propagated Unidirectionally without Diminution

At the peak of an action potential, passive spread of the membrane depolarization is sufficient to depolarize a “downstream” segment of membrane. This causes a few Na+ channels in this region to open, thereby increasing the extent of depolarization in this region, causing an explos-ive opening of more Na+ channels. Thus, propagation of the action potential without diminution is ensured.

Because voltage-gated Na+ channels remain inactive for several milliseconds after opening, those Na+ channels immediately “behind” the action potential cannot reopen even though the potential in this segment is depolarized due to passive spread (Figure 21-14). The inability of Na+ channels to reopen during the refractory period ensures that action potentials are propagated unidirectionally from the cell body to the axon terminus, and limits the number of action potentials per second that a neuron can conduct. Reopening of Na+ channels “behind” the action potential is also prevented by the membrane hyperpolarization that results from opening of voltage-gated K+ channels.

Figure 21-14. Unidirectional conduction of an action potential due to transient inactivation of voltage-gated Na+ channels.

Figure 21-14

Unidirectional conduction of an action potential due to transient inactivation of voltage-gated Na+ channels. At time 0, an action potential (purple) is at the 2-mm position on the axon. The membrane depolarization spreads passively in both directions (more...)

Movements of Only a Few Na+ and K+ Ions Generate the Action Potential

The changes in membrane potential characteristic of an action potential are caused by rearrangements in the balances of ions on either side of the membrane, not by changes in the concentrations of ions in the solutions on either side. The voltage changes are generated by the movements of Na+ and K+ ions across the plasma membrane through voltage-gated channels, but the actual number of ions that move is very small relative to the total number in the neuronal cytosol. In fact, measurements of the amount of radioactive sodium entering and leaving single squid axons and other axons during a single action potential show that, depending on the size of the neuron, only about one K+ ion per 3000 – 300,000 in the cytosol (0.0003 – 0.03 percent) is exchanged for extracellular Na+ to generate the reversals of membrane polarity.

As discussed previously, the resting membrane potential in nerve cells results primarily from the gradient of K+ ions that is generated and maintained by the Na+/K+ ATPase. This ATPase plays no direct role in impulse conduction. If dinitrophenol or another inhibitor of ATP production is added to cells, the membrane potential gradually falls to zero as all the ions equilibrate across the membrane. In large nerve cells such as in the squid this equilibration is extremely slow, requiring hours, but in smaller mammalian nerves this equilibration occurs in only 5 minutes. In either case, the membrane potential is essentially independent of the supply of ATP over the short time spans required for nerve cells to generate and conduct action potentials. Nerve cells normally can fire thousands of times in the absence of an energy supply because the ion movements during each discharge involve only a minute fraction of the cell’s K+ and Na+ ions.

Myelination Increases the Velocity of Impulse Conduction

In man, the cell body of a motor neuron that innervates a leg muscle is in the spinal cord and the axon is about a meter in length (see Figure 21-5). Because the axon is coated with a myelin sheath (Figure 21-15), which increases the velocity of impulse conduction, it takes only about 0.01 second for an action potential to travel the length of the axon and stimulate muscle contraction. Various myelinated neurons conduct action potentials at velocities of 10 to 100 meters per second (m/s). Without myelin the velocity would be ≈1 m/s, and coordination of movements such as running would be impossible.

Figure 21-15. Two views of the myelin sheath.

Figure 21-15

Two views of the myelin sheath. (a) Electron micrograph of a cross section of the axon of a myelinated peripheral neuron. It is surrounded by the Schwann cell (SN) that produced the myelin sheath, which can contain 50 – 100 membrane (more...)

Myelin is a stack of specialized plasma membrane sheets produced by a glial cell that wraps itself around the axon. In the peripheral nervous system, these glial cells are called Schwann cells; in the central nervous system, they are called oligodendrocytes. Often several axons are surrounded by a single glial cell (Figure 21-16a). In both vertebrates and some invertebrates, axons are accompanied along their length by glial cells, but specialization of these glial cells to form myelin occurs predominantly in vertebrates. Vertebrate glial cells that will later form myelin have on their surface a myelin-associated glycoprotein and other proteins that bind to adjacent axons and trigger the formation of myelin.

Figure 21-16. Formation and structure of a myelin sheath in the peripheral nervous system.

Figure 21-16

Formation and structure of a myelin sheath in the peripheral nervous system. (a) By wrapping itself around several axons simultaneously, a single Schwann cell can form a myelin sheath around multiple axons. As the Schwann cell continues to wrap around (more...)

A myelin membrane, like all membranes, contains phospholipid bilayers, but unlike many other membranes, it contains only a few types of proteins. The predominant myelin protein in the peripheral nervous system is Po, which causes adjacent plasma membranes to stack tightly together (Figure 21-16b). Myelin in the central nervous contains a cytosolic and a membrane protein, termed myelin basic protein and proteolipid, respectively, that together function similarly to Po.

The myelin sheath surrounding an axon is formed from many glial cells. Each region of myelin formed by an individual glial cell is separated from the next region by an unmyelinated area called the node of Ranvier (or simply, node); only at nodes is the axonal membrane in direct contact with the extracellular fluid (Figure 21-17). Because the myelin sheath prevents the transfer of ions between the axonal cytosol and the extracellular fluids, all electric activity in axons is confined to the nodes of Ranvier, where ions can flow across the axonal membrane. Glial cells secrete protein hormones that somehow trigger the clustering of Na+ channels at the nodes. As a result, the node regions contain a high density of voltage-gated Na+ channels (≈10,000 per square micrometer of axonal plasma membrane), whereas the regions of axonal membrane between the nodes have few, if any, Na+ channels. Na+/K+ ATPase, which maintains the ionic gradients in the axon, is also localized to the nodes. The fibrous cytoskeletal protein ankyrin binds to these proteins and keeps them in the nodal membrane.

Figure 21-17. Structure of a peripheral myelinated axon near a node of Ranvier, the gap that separates the portions of the myelin sheath formed by two adjacent Schwann cells.

Figure 21-17

Structure of a peripheral myelinated axon near a node of Ranvier, the gap that separates the portions of the myelin sheath formed by two adjacent Schwann cells. These nodes are the only regions along the axon where the axonal membrane is in direct contact (more...)

Myelinated nerves have length constants of several millimeters for passive spread of depolarization because ions can move across the axonal membrane only at the myelin-free nodes (see Figure 21-11). Thus the excess cytosolic positive ions generated at a node during the membrane depolarization associated with an action potential spread passively through the axonal cytosol to the next node with very little loss or attenuation, causing a depolarization at one node to spread rapidly to the next node. This permits the action potential to “jump,” in effect, from node to node (Figure 21-18). For this reason, the conduction velocity of myelinated nerves is about the same as that of much larger unmyelinated nerves. For instance, a 12-μm-diameter myelinated vertebrate axon and a 600-μm-diameter unmyelinated squid axon both conduct impulses at 12 m/s; the unmyelinated squid giant axon occupies several thousand times the space of this myelinated vertebrate axon and uses several thousand-fold more energy. Not surprisingly, myelinated nerves are used for signaling in circuits where speed is important. Evolution of the myelin sheath also allowed many more fast-conducting axons to occupy a smaller space, and clearly was essential for evolution of the vertebrate brain.

Figure 21-18. Regeneration of action potentials at the nodes of Ranvier.

Figure 21-18

Regeneration of action potentials at the nodes of Ranvier. (a) The influx of Na+ ions associated with an action potential at one node results in depolarization of that region of the axonal membrane. (b) Depolarization moves rapidly down the axon because (more...)

Image med.jpgOne of the leading serious neurologic diseases among human adults is multiple sclerosis (MS), usually characterized by spasms and weakness in one or more limbs, bladder dysfunction, local sensory losses, and visual disturbances. This disorder — the prototype demyelinating disease — is caused by patchy loss of myelin in areas of the brain and spinal cord. In MS patients, conduction of action potentials by the demyelinated neurons is slowed and the Na+ channels spread outward from the nodes. The cause of the disease is not known but appears to involve either the body’s production of autoantibodies (antibodies that bind to normal body proteins) that react with myelin basic protein or the secretion of proteases that destroy myelin proteins.

SUMMARY

  •  An electric potential exists across the plasma membrane of all eukaryotic cells because the ion compositions of the cytosol and extracellular fluid differ, as do the permeabilities of the plasma membrane to the principal cellular ions: Na+, K+, Cl, and Ca2+.
  •  In most nerve and muscle cells, the resting membrane potential is about 60 mV, negative on the inside; the potential is due mainly to the relatively large number of open K+ channels in the membrane (see Figure 21-9).
  •  Without voltage-gated cation channels, membrane depolarizations would spread passively only short distances (0.1 to about 5 mm) before the membrane potential returns to its original value.
  •  An action potential results from the sequential opening and closing of voltage-gated cation channels. First, opening of Na+ channels permits influx of Na+ ions for about 1 ms, causing a sudden large depolarization of a segment of the membrane. The channel then closes and becomes unable to open (refractory) for several milliseconds, preventing further Na+ flow (see Figure 21-13). Opening of K+ channels as the action potential reaches its peak permits efflux of K+ ions, which initially hyperpolarizes the membrane. As these channels close, the membrane returns to its resting potential.
  •  The depolarization associated with an action potential generated at one point along an axon spreads passively to the adjacent segment, where it triggers opening of voltage-gated Na+ channels and hence another action potential. Propagation of the action potential occurs in one direction only because of the short inactive period of the Na+ channels and the brief hyperpolarization resulting from K+ efflux (see Figure 21-14).
  •  Thick neurons conduct impulses faster than thin ones. Myelination increases the rate of impulse conduction up to a hundred-fold.
  •  In myelinated neurons, voltage-gated Na+ channels are concentrated at nodes of Ranvier. Depolarization at one node spreads rapidly with little attenuation to the next node, so that the action potential “jumps” from node to node (see Figure 21-18).
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