Saltatory conduction in myelinated nerves

In 1925 Lillie suggested that the function of the myelin sheath in vertebrate nerve fibres might be to restrict the inward and outward passage of local circuit current to the nodes of Ranvier, so causing the nerve impulse to be propagated from node to node in a series of discrete jumps. He coined the term saltatory conduction for this kind of process, and supported the idea with some ingenious experiments on his iron wire model. (An iron wire immersed in nitric acid of the right strength acquires a surface film along which a disturbance can be propagated by local circuit action; the mechanism has several features analogous with those of nervous conduction, for which it has served as a useful model.) The hypothesis could not be tested physiologically until methods had been developed for the dissection of isolated fibres from myelinated nerve trunks, which was first done by Kato and his school in Japan in about 1930. Ten years later Tasaki produced strong support for the saltatory theory by showing that the threshold for electrical stimulation in a single myelinated fibre was much lower at the nodes than along the internodal stretches, and that blocking by anodal polarization and by local anaesthetics was more effective at the nodes than elsewhere. In collaboration with Takeuchi, Tasaki also introduced a technique for making direct measurements of the local circuit current flowing at different positions, and this approach was subsequently perfected by Huxley and Stampfli.

The method adopted by Huxley and Stampfli (Fig. 6.3) was to pull a myelinated fibre isolated from a frog nerve through a short glass capillary mounted in a partition between two compartments filled with Ringer's solution. The fluid-filled space around the nerve inside the capillary was sufficiently narrow to have a total resistance of about 0.5 megohm, so that the current flowing longitudinally between neighbouring nodes outside the myelin sheath gave rise to a measurable potential difference between the two sides of the partition, which could be recorded with an oscilloscope. The records of longitudinal current showed (Fig. 6.4) that at all points outside any one internode the current flow was roughly the same both in magnitude and timing. However, the peaks of current flow were displaced stepwise in time by about one tenth of a millisecond as successive nodes were traversed. In order to determine the amount of current that flowed radially into or out of the fibre, neighbouring pairs of records were subtracted from one another, since the difference between the longitudinal currents at any two points could only have arisen from current entering or leaving the axis cylinder between those points. This procedure gave the results illustrated in Fig. 6.5, from which it is seen that over the internodes there was merely a slight leakage of outward current, but that at each node there was a brief pulse of outward current followed by a much larger pulse of inward current. The current flowing transversely across the myelin sheath is exactly what would be expected for a passive leak, while the restriction of inward current to the nodes proves conclusively that the sodium

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Axis cylinder

Fig. 6.3. Diagram of the method used by Huxley and Stampfli (1949) to investigate saltatory conduction in nerve. The nerve fibre is pulled through a fine hole about 40 ^m in diameter in an insulator by a micromanipulator. Current flowing along the axis cyclinder out of one node and into the other as indicated by the arrows causes a voltage drop outside the myelin sheath. The resistance of the fluid in the gap between the two pools of Ringer's solution being about half a megohm, the potential difference between them can be measured by the oscilloscope G connected to electrodes E on either side. The internodal distance in a frog's myelinated nerve fibre is about 2 mm.

system operates only where the excitable membrane is accessible to the outside.

The term 'saltatory' means literally a process that is discontinuous, but it would nevertheless be wrong to suppose that only one node is active at a time in a myelinated nerve fibre. The conduction velocity in Huxley and Stampfli's experiments was 23 mm/ms, and the duration of the action potential was about 1.5 ms, so that the length of nerve occupied by the action potential at any moment was about 34 mm, which corresponds to a group of 17 neighbouring nodes. In the resistance network equivalent to a myelinated fibre (Fig. 6.6), the values of Rn and R are such that the electrotonic potential would decrement passively to 0.4 between one node and the next. Since the size of the fully developed action potential is of the order of 120 mV, and since the threshold depolarization needed to excite the membrane is only about 15 mV, it again follows that the conduction mechanism works with an appreciable

Anaesthetic Effects Nerve Impulses
Fig. 6.4. Currents flowing longitudinally at different positions along an isolated frog nerve fibre. The diagram of the fibre on the right-hand side shows the position where each record was taken. The distance between nodes was 2 mm. From Huxley and Stampfli (1949).

safety factor, and that the impulse should be able to encounter one or two inactive nodes without being blocked. Tasaki showed that two but not three nodes which had been treated with a local anaesthetic like cocaine could indeed be skipped.

A simple experiment which deserves mention was performed by Huxley and Stampfli to demonstrate the importance of the external current pathway in propagation along a myelinated nerve fibre. The nerve of a frog's sciatic—gastrocnemius preparation was pared down until only one fibre was left (Fig. 6.7). Stimulation of the nerve at Pthen caused a visible contraction of a motor unit M in the muscle. The preparation was now laid in two pools of Ringer's solution on microscope slides A and B which were electrically

Gastrocnemius Toad

Fig. 6.5. Transverse currents flowing at different positions along an isolated frog nerve fibre. Each trace shows the difference between the longitudinal currents, recorded as in Fig. 6.4, at the two points 0.75 mm apart indicated to the right. The vertical mark above each trace shows the time when the change in membrane potential reached its peak at that position along the fibre. Outward current is plotted upwards. From Huxley and Stampfli (1949).

Saltatory Conduction

Fig. 6.6. Equivalent circuit for the resistive elements of a myelinated nerve fibre. According to Tasaki (1953), for a toad fibre whose outside diameter is 12 ^m and a nodal spacing 2 mm, the internal longitudinal resistance R is just under 20 MH and the resistance Rn across each node is just over 20 MH. In a large volume of fluid the external resistance Ro is negligibly small.

Fig. 6.6. Equivalent circuit for the resistive elements of a myelinated nerve fibre. According to Tasaki (1953), for a toad fibre whose outside diameter is 12 ^m and a nodal spacing 2 mm, the internal longitudinal resistance R is just under 20 MH and the resistance Rn across each node is just over 20 MH. In a large volume of fluid the external resistance Ro is negligibly small.

Myelinated Nerve Fiber Over Hemmorhage

Fig. 6.7. Method used by Huxley and Stampfli (1949) to demonstrate the role of the external current pathway in a myelinated nerve fibre. A, B, insulated microscope slides. SE, stimulating electrodes. P, proximal end of frog's sciatic nerve. D, distal end of nerve. M, gastrocnemius muscle. T, moist thread providing an electrical connection between the pools of Ringer's solution on the slides.

Fig. 6.7. Method used by Huxley and Stampfli (1949) to demonstrate the role of the external current pathway in a myelinated nerve fibre. A, B, insulated microscope slides. SE, stimulating electrodes. P, proximal end of frog's sciatic nerve. D, distal end of nerve. M, gastrocnemius muscle. T, moist thread providing an electrical connection between the pools of Ringer's solution on the slides.

insulated from one another, and its position was adjusted so that part of an internode, but not a node, lay across the 1 mm air gap separating the pools. At first, stimulation at P continued to cause a muscle twitch, but soon the layer of fluid outside the myelin sheath in the air gap was dried up by evaporation, and the muscle ceased to contract. Conduction across the gap could, however, be restored by placing a wet thread T between the two pools. This demonstrated that an action potential arriving at the node just to the left of the air gap could trigger the node on the far side of the gap only when there was an electrical connection between the pools whose resistance was fairly low. On reference to Fig. 6.6 it will be seen that if Ro becomes at all large, the potential change at N2 produced by a spike at N will fall below the threshold for excitation. As has been pointed out by Tasaki, a reservation needs to be made about this experiment. Unless special precautions are taken, the stray electrical capacity between the pools may provide, for a brief pulse of current, an alternative pathway outside the dried-up myelin of the internode whose impedance may be low enough for excitation to occur at the further node if its threshold is low. Even with such precautions, Tasaki found that impulses were still able to jump the gap if the fibre had a really low threshold, probably because simple evaporation could not make the external resistance high enough. Nevertheless, the fact that the experiment works in a clear-cut way only if the threshold is somewhat higher than it is in vivo does not prevent it from proving rather satisfactorily that there must be a low-impedance pathway between neighbouring nodes outside the myelin sheath if the nerve impulse is to be conducted along the fibre.

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