1. The Nerve Impulse:

     A rough overview of the nerve impulse was given in Chapter 4. A more complete presentation will be given here.

     The resting potential is characteristic of most cells, and nerves are no exception. The inside of the cell is electrically negative to the outside when the cell is at rest. The difference in charge is due to a combination of passive and active factors.

     The structural properties of the cell membrane are largely responsible for the "passive" charge. Sodium, which is positively charged, cannot move readily to the inside of the cell across the membrane, and in the same way, most of the negatively charged ions within the cell are retained by the membrane.

     The membrane is quite permeable to potassium and to chloride, but these are held inside and outside the cells, respectively, by the ions to which the membrane is not permeable. Thus potassium cannot escape from the intracellular anions, which are kept in place by the membrane; neither can chloride escape from the extracellular sodium which cannot enter the cell.

     In all probability, a little sodium enters cells even at rest and is replaced by potassium. Through active transport, this sodium is rejected by the cell and potassium is exchanged for it. Nevertheless, the membrane tends to leak a little potassium to the outside which makes the outside of the fiber positively charged. A little chloride leaks to the inside, exaggerating the voltage difference.

     Figure 162 shows the distribution of ions across a resting membrane. There is only a slight imbalance of ions, but it is enough to make a very sizable voltage. The voltage in most nerves is about 0.07 V, or 70 millivolts.

     The initiation and propagation of the nerve impulse involve sudden changes in sodium conductance. It has been speculated that the movement of sodium occurs through channels lined by molecules which ordinarily prevent such movement. When the membrane is stimulated a little--but not enough to initiate the impulse--the molecules which line the channels begin to change in such a way that sodium movements become more possible. A stimulus adequate to excite "clears the way" for sodium entirely. The reader may be helped in visualizing this if he imagines a car tunnel obstructed by fallen concrete. A car can still make its way through the tunnel, but slowly, since it must go around the chunks of concrete. As the concrete is cleared, the passage of the car through the tunnel is made more rapid, but complete clearance is required for normal rates of travel.

     In the case of nerve, the equivalent of partial clearage can be accomplished electrically by applying a fixed voltage across the nerve. The application of a negative potential to the outside seems to achieve this and makes nerve stimulation much easier.

     Sudden increases in sodium permeability occur almost explosively when the stimulus is adequate to excite. Sodium flows into the cell almost without hindrance, but the potassium channels are suddenly blocked. Even as the sodium flows, it seems to disrupt the channels through which it has flowed. Very soon these channels no longer exist, and sodium, now within the cell, has no easy way out. The fact that potassium channels are blocked results in an excess of positive ions within the cell, a complete reversal of the normal condition.

     The blocked potassium channels now open very rapidly. At about the same time, the sodium rejection mechanism referred to above, the sodium pump, comes into operation, and very soon the resting conditions are restored in the activated portion of the nerve.

     It should be stressed here that very small quantities of sodium and potassium actually move in the processes described above. For example, in a small nerve fiber 0.1 micra in diameter, about 100 sodium and potassium ions move in each stimulated millimeter. The large voltages that develop from the movement of so few ions may come as a surprise, but the fact is that small charge displacements result in huge voltages.

     Once an area has become excited, the further propagation of the impulse is easily understood. The local electrical disturbance serves as a source of current flow from undisturbed regions. These, in turn, are activated by the current flow, and themselves disturbed, they show the same electrical changes and disturb adjacent regions.

     An important exception must be made. Disturbance of a single portion of a cell may not lead to enough current density in the adjacent parts to stimulate them. Thus, ordinarily, depolarization in the area of one synapse will not cause neuronal discharge, but when a substantial part of the neuron is depolarized, such discharge will occur. Local depolarizations in the neuromuscular junction do not ordinarily discharge the muscle unit.

2. The Neuromuscular Junction:

     The connection between the nerve fibers of skeletal muscle and the muscle units supplied by them is by way of the neuromuscular junction. This has been mentioned briefly before (Chapter 4). It has been calculated that there is no possibility at all that the nerve impulse can get to the muscle electrically. On the other hand, it has been shown quite convincingly that the terminal of the nerve fiber contains pre-formed acetyl choline. Small quantities of this material are released in a random manner at all times. The nerve impulse co-ordinates this release, especially if sufficient calcium is present. When this happens, the muscle receptor sites for acetyl choline are suddenly filled, and the muscular side of the neuromuscular junction shows the same kind of ionic transfer just referred to, where sodium moves into the cells while potassium moves out. These ionic movements change the "end plate potentials," which when they reach critical size, propagate through the muscle unit.

     Curare, blocking sites ordinarily available to acetyl choline, abolishes the end plate potential by preventing ionic movements. Anticholinesterases, by preventing acetyl choline destruction, tend to increase end plate potentials and prolong them in time. The reversible anticholinesterases--stigmine and neostigmine--are useful in treating diseases where acetyl choline synthesis is impaired. The irreversible ones, like DFP and the nerve gases, are quite likely to produce fatal paralysis.

3. Properties of Skeletal Muscle:

     Many of the properties of skeletal muscle were discussed in Chapters 3 and 4. It should be emphasized here that most of these properties apply primarily to skeletal muscle. Smooth and cardiac muscles behave very differently.

4. Properties of Smooth Muscle:

     Two types of smooth muscle are recognized: the multi unit type and the visceral type, the latter behaving as a syncytium. Both types are characterized by the presence of spindle shaped non-striated cells. The typical visceral smooth muscle cell is 4 to 8 micra in diameter at the center, and 50 to 200 micra in length. Many such cells are packed into bundles, the cells of these bundles usually being connected by small intercellular bridges.

     The neuromuscular junction in smooth muscle differs radically from its counter part in skeletal muscle. The nerve fibers are transmission fibers, usually unmyelinated. The fibers are usually quite small (0.1 - 0.2 u) and transmission of the nerve impulse through them is very slow. The nerve fibers are extensively branched; from time to time a branch may come into contact with a muscle cell, but the intimacy of contact seen in the neuromuscular junction of skeletal muscles is never seen.

     The membrane potential in smooth muscle is generally smaller than that of skeletal muscle. It varies almost randomly with time. Sudden stretch of smooth muscle at any point usually tends to depolarize it and sudden stretch is one of the most effective stimuli for smooth muscle. Acetyl choline, released by cholinergic nerve endings, tends to depolarize smooth muscle. The effects of epinephrine on the polarization of smooth muscle are variable. There is no particular concentration of cholinesterase at the junction of smooth muscle with its nerve fibers. Thus acetyl choline and cholinergic drugs in general are much more effective in producing smooth than striated muscle contraction, and, in fact, the transmitters produced at one smooth muscle site may be effective at other smooth muscle sites as well.

     Smooth muscle is slow. Its latent period is long and its contractions may be extremely sluggish. Contraction may be maintained over long periods with almost no expenditure of energy. This is easily understood, for the shortening of smooth muscle probably results from the sliding of filaments, just as in skeletal muscle. The bonds between the filaments do not break down, so the muscle remains contracted.

     Just as smooth muscle can remain shortened without energy expenditure, it can be easily elongated without developing tension, provided that the elongation is not so sudden as to change the membrane potential.

     Smooth muscle appears to be able to accomplish its function through its nerves, chemical changes, stretch, and perhaps its own control (autonomically). It may be the case that smooth muscle systems which, as mentioned, have highly variable membrane potentials may respond to a spontaneous electrical change in a part of the muscle which, for the time being, is the "pacemaker" of the muscle. The pacemaker may shift its anatomical location or alter its frequency of discharge. However, the function of the muscle is usually preserved. Denervation of smooth muscle reduces its function in any important way, and as has been mentioned before, it may actually produce hypersensitivity.

5. Properties of Cardiac Muscle:

     Heart muscle, which shows cross striations like skeletal muscle, is innervated like smooth muscle. In some important respects it differs from both. The most important characteristic of the heart from the functional standpoint is that it behaves as a syncytium, producing a fast propagation of the impulse. Striated muscle is divided into motor units and most smooth muscles respond slowly. Actually there are two syncytial masses, the atria making one, and the ventricles, the other. The cardiac impulse ordinarily originates in one place and spreads in a characteristic way. Like smooth muscle, the action of the heart can be independent of nerves, though modified by them. Unlike smooth muscle, the random variations in membrane potential do not occur.

     The action potentials of the heart show another interesting property. Depolarization is much longer in heart muscle than in skeletal muscle; in fact it lasts throughout the contraction. Repolarization at the pacemaker is of very short duration, and depolarization begins almost as soon as the muscle is repolarized. These and other properties of the heart will be discussed again in Chapter 10.

Continue to Chapter 8.