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J. Physiol. (I952) iI8, I07-I12

SALTATORY CONDUCTION IN MYELINATEDNERVE FIBRES

BY BERNHARD FRANKENHAEUSERFrom the Nobel Institute of Neurophysiology, Karolinska Institutet,

Stockholm

(Received 10 March 1952)

The impulse conduction in a myelinated nerve fibre has been held by someinvestigators to be 'saltatory' in the sense that the activity jumps from nodeto node (for references see Tasaki & Takeuchi, 1942; Huxley & Stiimpfii,1949; Frankenhaeuser & Schneider, 1951), whereas others hold it to becontinuous (Lorente de N6, 1947; Laporte, 1951). For detailed informationconcerning the evidence in favour of saltatory conduction in isolated nervefibres reference is made to the recent reviews by Huxley & Stiimpffi (1949),Hodgkin (1951) and Frankenhaeuser & Schneider (1951). This evidence seemsfully convincing. Recently, however, it has been suggested that conduction inan undissected fibre is a continuous process (Laporte, 1951). If conduction inan intact fibre is continuous but in a dissected fibre saltatory, it is impossibleto apply the results obtained on isolated fibres to undissected fibres. Con-sequently, it is of prime importance for the understanding of the activity ofperipheral nerve to clear up this discrepancy.

Laporte's evidence for continuous conduction in an undissected nervefibre is summarized in the statement that 'the conduction time increasescontinuously and linearly with increasing conduction distance, the spikedisplays constant magnitude and shape when the recording electrode isdisplaced along the nerve, and the spike presents no signs of fractionation'.Laporte experimented on carp and frog nerves. The action potential wasusually recorded with an inter-electrode distance of 9-20 mm with oneelectrode on the killed end of the nerve. The longitudinal current was in someexperiments recorded with 1*5 mm inter-electrode distance. Laporte drewthe conclusion that the conduction of impulses in peripheral myelinatedfibres of a nerve trunk is a continuous process.

Stiimpffi & Zotterman (1951) experimented on single fibres with intactconnective tissue sheath. They found that the slope of the rise of the actionpotential varied with the electrode positions in a regular manner, and fromthis concluded that conduction is saltatory. Their experiments certainly

108 BERNHARD FRANKENHAEUSER

favour the assumption that conduction in intact fibre is saltatory. As pointedout, the question whether conduction is continuous or saltatory is of primeimportance for the understanding of the activity in peripheral nerve. For thisreason it seemed worth while to look for more direct evidence in order tosettle this question.Whether conduction is continuous or saltatory, an active region should

always be characterized by an inward direction of the membrane current(Huxley & Stiimpffi, 1949). In an isolated myelinated fibre the nodes ofRanvier are the only places where an inward current can be observed (Tasaki &Takeuchi, 1942; Huxley & Stampfli, 1949).

In the present investigation it will be shown that an undissected myelinatedfrog fibre with intact connective tissue sheath displays likewise inwardcurrent at certain points only along its course. From this it is concludedthat conduction must be saltatory and not continuous.

METHODS

Preparation. The experiments were carried out on a small nerve twig from the sciatic nerve ofRana temporaria. This twig is regularly found just distal to the point where the tibial and peronealnerves separate. This preparation contains only about five large myelinated fibres and a numberof small fibres. The nerve is easily dissected free from surrounding loose connective tissue andthen provides a slender homogeneous preparation of about 5 mm length. The distal end of thenerve was left intact in the tissue, the sciatic trunk was dissected free and cut centrally, and all

other branches were cut.Stimulation and recording. The preparation was mounted in a box made of plexiglas (methyl

methacrylate polymer) (Fig. 1). The whole preparation was kept immersed in Ringer solution.The sciatic trunk was sealed with petroleum jelly at partitition1 in order to obtain an increasedresistance outside the nerve and thus keep the stimulating current reasonably low. The nerve

twig was sealed at partitions 2 and3 in order to obtain a high ohmic recording resistance. Itshould be noted that partitions 2 and 3 and the fluid gap between them are each 0-25 mm.

Attention is also drawn to the fluid shunt between the Ringer pools on either side of the recordingresistance. This arrangement records the membrane current, i.e. the transversal current throughthe membrane, as a difference between the longitudinal currents at two neighbouring segments.This part of the argument has been clarified by Tasaki & Takeuchi (1942) and Huxley & Stampfli(1949).Ag-AgCl electrodes were used for stimulation and recording. The nerve was stimulated every

3 sec with a short rectangular pulse from a flip-flop stimulator, synchronized with the time base.The activity in the nerve was recorded with aR.c. coupled amplifier with a flat frequency

response (± 1 decibel) from about 20c/s to 80 kc/s. Cathode followers were used as input stage.

A cathode-ray tube and continuouslyrunning photographic paper were used in the conventionalmanner.The nerve twig was sealed in its proximal end at partitions 2 and 3 (Fig. 1) and moved by hand

to and fro under microscopic control in a longitudinal direction through the recording site. Thenerve twig was not touched by the needles used to grasp the preparation. The nerve moved easilyin the recording site. When the movement was not quite longitudinal the channels inthe petroleumjelly became wider as observed through the microscope, and the amplitude of the recordedpotential decreased as a result of the decreased recording resistance. As far as possible stretchingof the nerve was avoided. Stretches somewhat greater than any likely to be sustained did notaffect the results.

SALTATORY CONDUCTION

RESULTS

In the present experiments a single fibre was activated by each stimulus.Single fibre response was obtained either by adjusting the stimulus strengthso that one fibre alone was activated or else by dissecting the nerve trunkproximal to the branch. Both methods gave the same result. The longitudinalcurrent was recorded (fluid shunt removed, Fig. 1) when the conventionalcontrols for a single fibre response were made. It proved to be diphasic overthe whole stretch of nerve used in the experiments.

It was expected that the recording resistance would decrease when thenerve was moved in the channels formed in the petroleum jelly at the recordingsite. This happened, however, only the first time the nerve was moved. Afterthe first move the spike had practically constant amplitude when recordedfrom the same place before and after several movements. This finding showsthat the recording resistance is stable enough for the investigation.The membrane current was recorded while the nerve was moved in steps

in the recording site under the microscope. An outward current (a deflexionupward from the base-line) was recorded from all parts of the nerve (Fig. 2 a-g).In most places this was not followed by any other deflexion (b, c and e),but in some records (a, d and g) it was followed by an inward current. Thusthese places with inward durrent are the only places where generation ofaction current takes place. The active regions are regularly spaced at about1 mm which is the expected internodal length of this fibre. Each segmentbehaved in a constant manner throughout the experiment with respect tothe direction of the current.

DISCUSSION

The experiments clearly show that in an undissected myelinated nerve fibrewith intact connective tissue sheath there is inward membrane current atsome points only, whereas the recorded current at other points is exclusivelyoutward in direction. The points with inward current are spaced as the nodesare expected to be spaced. Evidently these fibres behave in a similar mannerto isolated fibres. Therefore it is concluded that the impulse conduction in theundissected myelinated fibre is saltatory. This is the standpoint taken up byStaimpffi & Zotterman (1951). It is, however, in sharp disagreement with theconclusion drawn by Laporte (1951).

Let us now inquire into the reason for this discrepancy. Laporte, as stated,based his conclusions upon the observations that 'conduction time increasescontinuously and linearly with increasing conduction distance, the spikedisplays constant magnitude and shape when the first recording electrode isdisplaced along the nerve, and the spike presents no signs of fractionation'.

Laporte made his principal observations on the monophasic action potentialrecorded with an inter-electrode distance of 16-5-19-5 mm (frog nerve). The

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110 BERNHARD FRANKENHAEUSER

Fig. 1. Diagram of stimulation and recording. The nerve is sealed with petroleum jelly at thepartitions 1-3. Partitions 2 and 3 and the fluid gap between them are each 025 mm.Insulation is indicated by oblique lines; petroleum jelly seal indicated in lower figure byvertical lines. The figure is not drawn to scale.

a 4>4tiL^4

c wrd

e

gI, VW~~~~~~~~- Wt1

Fig. 2. Membrane current recorded from the nerve twig, the recording site moved in distaldirection about 03 mm between each record. Inward current downwards. The verticallines indicate the time for the peak of the outward current in records a, d and g. Longitudinalcurrent of 'binodal' type during the whole experiment. Time 10,000 c/s.

SALTATORY CONDUCTION

time for the rise of the action potential recorded with this large inter-electrodedistance is 036 msec as measured from foot to peak in Laporte's fig. 5. Theconduction rate was 31 m/sec; therefore the impulse had moved 11-3 mmduring this time. Evidently 11-3 mm of fibre participates in the measurablepart of the rise of the action potential. If only the steep rising part of theaction potential is taken into consideration, the impulse has lasted 0-18 msecand has moved 5-5 mm. These figures show that a stretch of more than oneinternode had been activated during the rising phase.

Let us assume conduction to be saltatory. Applying Ohm's law it is easilyfound that the longitudinal current caused by the activity of one node close tothe recording electrode participates in the recorded action potential to anextent depending upon the external recording resistance of this current loop(Fig. 3). This recording resistance is altered when the electrode is movedalong the nerve. The time interval from the stimulus artifact to the foot or tothe peak should thus be expected to change continuously and more or less

-_ 7'-s{ r{ ]1 2 3

Fig. 3. Principal current spread when node 1 is active (saltatory conduction). The currentthrough nodes 4, 5, . . ., and through the myelin sheath is neglected. External conductor isassumed to be a homogeneous cylinder. Left electrode is moved along the nerve from rightto left.

linearly and the action potential to have nearly constant amplitude when theelectrode is moved along the fibre. This is exactly what Laporte found. Theseobservations, however, do not help to settle the question whether conductionis continuous or saltatory (cf. Stampffi & Zotterman, 1951; Huxley, 1951)since each is bound to produce a continuous change.The time interval between the start of activity in two neighbouring nodes

is about 005 msec as calculated from conduction rate and internodal distance.If we wish to measure this time interval the measuring must be done onthose points of the action potential at which the activity actually starts inthe nodes concerned. This value can theoretically be obtained from recordsof the action potential provided that the recording apparatus has a frequencyresponse high enough to record the variations in slope of the rising phase ofthe action potential as described by Staimpfli & Zotterman (1951). Thetracings these authors present in their fig. 3 do not, however, allow this timeinterval to be calculated because the tracings are either not mounted for thatpurpose, or the latency has varied in the course of the experiment (stimulusstrength near threshold?). Laporte has, evidently, to judge from the noiselevel, used an amplifier with a too narrow frequency band in the high

ill

BERNHARD FRANKENHAEUSERfrequencies and thus has not been able to record the expected changes inthe action potential.

In the present investigation the membrane current was recorded. In suchrecords we have, in the peak of the outward current, an approximate land-mark for the beginning of activity at the recording site, and, in the peak ofthe inward current, a similar landmark for the beginning of activity in thenext segment of the fibre. From Fig. 2 in this paper it is evident that thesepoints fit in with what is expected if conduction is saltatory but do not agreewith continuous conduction.The absence of fractionation of the recorded potentials is not a strong

argument against the saltatory conduction theory, particularly ifthe potentialsare recorded so that the spikes are rounded off in the amplifier system.Fractionation may be more pronounced in dissected fibres, partly becausethese fibres may to some extent have been damaged during the dissection,and partly because the recording resistance can be made shorter with dissectedfibres. The aim of the present investigation is only to show that conduction isalso saltatory in undissected nerve fibre, and not to consider how far thedissected fibre is altered in its properties in other respects.Thus we have seen that none of Laporte's findings gives any information

whatsoever about the question whether conduction is continuous or saltatory.Stampifi & Zotterman (1951) held conduction in intact fibre to be saltatory onthe evidence that the slope of the rising part of the action potential varies ina regular manner. In the present investigation it was shown that an inwardmembrane current is recorded from some points only along the intact nervefibre. Therefore we conclude that conduction in peripheral myelinated fibresis saltatory independently of whether the fibre is dissected or intact.

SUMMARY1. It has been shown that an undissected myelinated frog fibre displays

inward membrane current at certain points only along its course.2. The conclusions drawn by Laporte (1951) are criticized.3. It is concluded that conduction is saltatory independently of whether

the fibre is dissected or intact.The experiments have been supported by a grant to the laboratory from the Rockefeller

Foundation.REFERENCES

Frankenhaeuser, B. & Schneider, D. (1951). J. Phy8iol. 115, 177.Hodgkin, A. L. (1951). Biol. Rev. 26, 339.Huxley, A. F. (1951). Cited by Hodgkin, A. L. in Biol. Rev. 1951, 26, 396.Huxley, A. F. & Stampfli, R. (1949). J. Phy8iol. 108, 315.Laporte, Y. (1951). J. gen. Phy8iol. 35, 343.Lorente de No, R. (1947). A study in nerve physiology, pt. 2, pp. 68-74. Stud. Rockefeller Int.

med. Re8. 132.St&mpffil, R. & Zotterman, Y. (1951). Helv. phy8iol. acta, 9, 208.Tasaki, I. & Takeuchi, T. (1942). Pflug. Arch. gee. Phy8iol. 254, 764.

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