Neurophysiology of Extraocular Muscles

Neurophysiology of extraocular muscles

Paul Bach-y-Rita

Physiological properties of extraocular muscle fibers are discussed. Several morphological types of fibers are present in these muscles. Studies on fast singly innervated twitch fibers and on slow multi-innervated fibers suggest that the properties of the former are consistent with "phasic" functions, and those of the latter are consistent with "tonic" functions.

Ely.e movements may be divided grossly fibers may have multiple motor endings. into "tonic" and "phasic" movements. Are Recent studies0 have shown that at least both of these principal types produced by three moq^hological types of fibers are the same motor nerves and muscle fibers, found in cat eye muscles, including one or are separate systems present that are type characteristic of very fast twitch functionally suited to each of the types of fibers, one characteristic of slower twitch movements? Morphological and physiolog- fibers, and one resembling typical multi- ical studies demonstrate that at least two innervated fibers. and possibly three neuromuscular systems In rabbit eye muscles, Matyushkin7's has are present in eye muscles, and that these recorded from one type of "phasic" and two have characteristics which would suit them types of "tonic" fibers. He was able to for different types of eye movements. record action potentials only from the Hess and Pilar1 have shown that cat "phasic" fibers. Bach-y-Rita and I to0 have extraocular muscles contain singly inner- recorded propagated overshoot action vated twitch fibers with "en plaque" type potentials from two types of twitch fibers: motor endings, and smaller multiply inner- the large fast singly innervated, and the vated "slow" fibers with endings analogous slow multi-innervated fibers. to "en grappe" motor endings. In human The two twitch fiber types are distin- eye muscles, cholinesterase staining tech- guished by their impulse conduction veloci- niques have been employed to demonstrate ties, their range of membrane potentials, these two fiber types as well as fibers with the amplitudes and frequencies of their multiple "en plaque" endings.2"5 miniature end plate potentials, their re- Kupfer'1 estimated that two thirds to sponses to the intravenous administration three quarters of all the extraocular muscle of succinycholine; by the velocities of conduction of the innervating nerve fibers; and by the frequency of stimulation required From the Institute of Visual Sciences, Presbyterian to produce fused tetanus of each type of Medical Center, San Francisco, Calif. fiber. The studies leading to these conclu- Partially supported by the National Institutes of sions have been published in detail else- Health Career Program Award No. 5 K3 where.9 NB 14,094 and the National Institutes of Health Research Program Project Grant No. 5 POl The methods used for recording from NB 06038. cat eye muscles are illustrated in Figs. 229

Downloaded from iovs.arvojournals.org on 10/01/2021 232 Bach-y-Rita Investigative Ophthalmology June 1967

I 1 mV

I20 mV

I 1 mV

20 mV

i i 2 msec Fig. 3. Intracellular records of responses in slow (parts A and B. bottom lines) and fast (parts C and D, bottom lines) muscle fibers of an inferior oblique muscle, in comparison with the extracellular responses displayed on the zero volt reference line (top lines). A, Anode break excitation followed by a long latency overshoot spike when the membrane potential was 68 mv. 73, A nonoveishoot response when the membrane potential (same fiber as in A) had decreased to 45 mv. C, A short latency overshoot spike response to maximal nerve stimulation (cathode excitation) in the fas~t fiber. D, No response to an anode break excitation in the same fiber as C. Parts A and C have been retouched with dashed lines. (Reprinted by permission of The Rockefeller University Press from The Journal of General Physiology, July, 1966,49: No. 6, 1177-1198.)

tude distribution suggests that the micro- Thus, they are polyneuronally innervated electrode picks up activity from the nearest as well as multi-innervated. end plate (largest amplitude), as well, as Mechanical studies show that the rise from nearby end plates (smaller ampli- time and total time course of a twitch tudes ). produced by the multi-innervated twitch Intracellular stimulation, through an im- fibers was much longer than the twitch of paling microelectrode, of each type of the fast fibers (Fig. 4). The fusion fre- fiber showed that localized depolarization quency was over 400 per second for the can produce propagated overshoot action fast, and approximately 25 per second for potentials in both types of fibers. Thus, the slow multi-innervated twitch fibers. activation of more than one end plate of In order to study the differential action the multi-innervated twitch fibers may not of a depolarizing (noncompetitive) block- be necessary to produce propagated im- ing agent on the extraocular muscle fibers, pulses. A study of the percentage of fibers intravenous succinylcholine was adminis- activated after cutting two thirds of the tered. Fig. 5 illustrates the contracture nerve to the muscle has suggested that the produced by the multi-innervated muscle multi-innervated muscle fibers receive fibers, and the inhibition of the tetanic nerve endings from more than one fiber. response. The multi-innervated fiber con-

Downloaded from iovs.arvojournals.org on 10/01/2021 Volume 6 Number 3 Physiology of extraocular muscles 233

tracture reached maximum earlier and re- be identified histologically.0 Some of these covered more quickly than the inhibition muscle types may not produce overshoot of the tetanic response, which developed propagated action potentials. In our studies, more slowly and greatly outlasted the con- these responses were not differentiated tracture. These results are in agreement from the decayed slow multi-innervated with those reported in this symposium by twitch responses. Clinical electromyo- Katz.10 graphic (EMG) studies on extraocular The physiology of extraocular muscles muscles are undertaken with extracellular is, however, more complex than the present needle electrodes, and undoubtedly do not studies indicate, since at least three and record activity from muscle fibers which possibly more types of muscle fibers can do not produce overshoot propagated action potentials. Cat extraocular muscles include one that is not found in man or in higher mammals: the retractor bulbi. A study of this muscle revealed that only fast twitch fibers ("phasic" type) are present.11'12 This would be in keeping with the role of this muscle: to retract the globe as part of a protective reflex involving the protrusion of the nictitating membrane. Thus, in the cat, the recti and obliques, which have ig i both "tonic" and "phasic" functions, contain both types of fibers, whereas the retractor 40 msec bulbi, which has "phasic" functions, con- Fig. 4. Isometric twitches in response to nerve tains only fast "phasic" fibers. stimulation of the inferior oblique muscle. The The foregoing studies suggest different proximal and central branches of the nerve have roles for each of the two twitch fiber types been cut, leaving only the distal branch intact. Initial tension 5.5 g. Upper line, a single twitch of present in the recti and oblique muscles. fast fibers selectively stimulated by a threshold The results suggest that the end plate cathode excitation to the nerve. Lower line, a potentials in slow fibers may attain the single twitch of slow fibers, selectively stimulated overshoot spike threshold with the summa- by anode break excitation. (Modified and reprinted by permission of The Rockefeller Uni- tion of less quanta than in fast fibers. In versity Press from The Journal of General addition, the fusion frequency of the slow Physiology, July, 1966, 49: No. 6, 1177-1198.) twitch fibers is lower than for the fast

i 1 10 sec Fig. 5. Isometric contracture produced by succinylcholine, and the simultaneous decrease in amplitude of the tetanic contraction. Initial tension 2.6 g. A, Before the administration of succinylcholine; maximal nerve stimulation at 350 per second for 150 msec, which produced maximal tetanic tension, was delivered at the rate of 0.13 per second. B, After the administration of succinylcholine; 250 /ig in a 2.7 kilogram cat, injected in the femoral vein at the beginning of the trace (arrow). (Reprinted by permission of The Rockefeller University Press from The Journal of General Physiology, July, 1966, 49: No. 6, 1177-1198.)

Downloaded from iovs.arvojournals.org on 10/01/2021 234 Bach-y-Rita Investigative Ophthalmology June 1967

fibers. It thus appears that neuromuscular ocular muscle by electron microscopy and transmission in slow twitch fibers is an cholinesterase staining, INVEST. OPHTH. 4: efficient mechanism for "tonic" muscle 51, 1965. 4. Kupfer, C.: Motor innervation of extraocular activity (which may include pursuit move- muscle, J. Physiol. 53: 533, 1960. ments, version movements, and possibly 5. Wolter, J. R., and O'Keefe, N. T.: Localiza- the slow phase of vestibular nystagmus), tion of nerve endings in relation to cholin- as well as for maintaining contraction of esterase deposits in normal human eye the eye muscles. However, some of these muscles, INVEST. OPHTH. 2: 558, 1963. functions may also be mediated by the 6. Peachey, L. D.: INVEST. OPHTH. 7. Matyushkin, D. P.: Phasic and tonic neuro- slow multi-innervated "felderstruktur" type motor units in the oculomotor apparatus of fibers. The tonic discharges recorded on the rabbit, Sechenov. Physiol. J. U.S.S.R. 47: electromyography (EMG) of extraocular 65, 1961. muscles, even during rest, could be pro- 8. Matyushkin, D. P.: Varieties of tonic muscle duced by the slow multi-innervated twitch fibers in the oculomotor apparatus of the rabbit, Bull. Exper. Biol. & Med. (U.S.S.R.) fibers since the present experiments show 55: 235, 1964. they are capable of producing spikes 9. Bach-y-Rita, P., and Ito, F.: In vivo studies which, with present EMG techniques, are on fast and slow muscle fibers in cat extra- indistinguishable from those produced by ocular muscles, J. Gen. Physiol. 49: 1177, the fast innervated fibers. 1966. 10. Katz, R., and Eakins, K. E.: Pharmacological REFERENCES studies of extraocular muscles, INVEST. OPHTH. 6: 261, 1967. 1. Hess, A., and Pilar, C: Slow fibers in the 11. Bach-y-Rita, P., and Ito, F.: In vivo micro- extraocular muscles of the cat, J. Physiol. electrode studies of the cat retractor bulbi 169: 780, 1963. fibers, INVEST. OPHTH. 4: 338, 1965. 2. Cheng, K.: Cholinesterase activity in human 12. Steinacker, A., Bach-y-Rita, P., and Alvarado, extraocular muscles, Jap. J. Ophth. 7: 174, G.: In vitro effect of succinylcholine on cat 1963. retractor bulbi, INVEST. OPHTH. (Abst., in 3. Dietert, S. E.: The demonstration of dif- press). ferent types of muscle fibers in human extra-

Downloaded from iovs.arvojournals.org on 10/01/2021