24 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



much greater than those of the exciting cause. . . ."'^ 

 Fontana (loS) went on to a recognition of the re- 

 fractory period (a term introduced by Marey) in 

 heart muscle which he explained as an exhaustion 

 of irritability resulting from the contraction. 



That skeletal muscle might share this property 

 was also foreshadowed by Fontana but did not receive 

 experimental proof until the work of Fick (109), an- 

 other pupil of Ludwig's, although the finding was 

 not further developed until the ingenious experi- 

 ments of Keith Lucas (no) at the beginning of this 

 century. In the meantime, an all-or-nothing property 

 in nerve had been detected by Gotch (m), the 

 predecessor of Sherrington in the Chair of Physiology 

 in Liverpool, a finding that was to reach definitive 

 form in the hands of Keith Lucas' pupil, Adrian (i 12, 

 113). That the law applied to sensory as well as to 

 motor nerves was established by Adrian & Forbes 

 (114) in 1922 (in a paper whose title replaced the 

 term 'all-or-none' by the more grammatical one 

 'all-or-nothing'). This line of work led on to investi- 

 gations of the refractory period of peripheral nerve 

 and the accurate plotting of the time course of after 

 potentials. The invention of the vacuum tube ampli- 

 fier and the cathode ray oscillo.scope opened the 

 modern era of electrophysiology, and with them the 

 foundations of today's techniques were laid by 

 Gasser & Erlanger (i 15). 



One branch of peripheral nerve physiology remains 



108. Fontana, Felice Caspar Ferdinand (1730-1805). De 

 Legibus Irritabilitatis. Lucca : Riccomini, 1 767. 



109. Fick, Adolf (1829- 1901). Mechanische Arbeit und Wurme- 

 fntivicklung bei der Miiskelthritigkeit. Leipzig: Brockhaus, 

 1882. 



1 10. Lucas, K. The "all-or-nonc" contraction of ampiiibian 

 skeletal muscle. J. Physiol. 38: 113, igog. 



111. Gotch, Francis (i853-igi3). The sub-maximal electrical 

 response of nerve to a single stimulus. J. Phyuol. 28: 



395. 1902- 



112. Adrian, Edgar D. (i88g- ). On the conduction of 

 subnormal disturbances in normal nerve. J. Physiol. 43: 

 389, 1912. 



113. Adrian, E. D. The "all-or-none" principle in nerve. J. 

 Physiol. 47: 460, 19 1 4. 



114. .Adrian, E. D. and A. Forbes. All-or-nothing responses 

 in sensory nerve fibres. J. Physiol. 56: 301, 1922. 



115. Gasser, Herbert S. (1888- ) and Joseph Erlanger 

 (1874- ). A study of the action currents of nerve 

 with a cathode ray oscillograph. Am. J. Physiol. 62: 496, 

 1922. 



" Quoted from Hoff, H. E. The history of the refractory 

 period. Yale J. Biol. & Med. 14: 635, 1942. 



to be outlined. This is the subject of neuromu.>;cular 

 transmission. Its history is short for, before the latter 

 half of the nineteenth century, continuity between 

 nerve and muscle was assumed, the neuron theory 

 had not been formulated and neuroneural synapsis 

 had not been conceived. The i 700-year-old hypothe- 

 sis of a nervous fluid implied humoral transmission in 

 structures having continuity and only at mid-nine- 

 teenth century, when this was finally abandoned, did 

 the possibility of junctional tissues become a live one. 



In 1862 Willy Kiihne (116, 117), pupil of von 

 Briicke and later professor of physiology in Heidelberg, 

 published a memoir on the end organs of motor nerves. 

 Noting the histological differences between muscle 

 and its innervating ner\e, he suggested that action 

 currents of the nerve by invasion of the muscle 

 caused it to contract. That there was a delay at the 

 neuromuscular junction was noted in du Bois-Rey- 

 mond's laboratory and the master him.self considered 

 the possibility of a chemical influence (the agents he 

 mentioned were ammonia and lactic acid which 

 Leibig had demonstrated in muscle in 1847); he went 

 to great pains, however, to sketch electrical fields in 

 support of what was called the 'modified discharge 

 hypothesis' (as shown in fig. i 7). 



The controversy surrounding the mode of trans- 

 mission at the motor end plate was carried into the 

 modern era and, at a time not yet history, essential 

 agreement was reached that transmission at the neuro- 

 muscular junction is chemical in nature. The major 

 contribution that settled the issue came from pharma- 

 cological experimentation of today's scientists, stem- 

 ming from the pioneer work of Elliott (118), Dale 

 (119) and Loewi (120) in the early part of the cen- 

 tury. Elliott, while a student at Cambridge, noticed 

 that smooth muscle responded to adrenin even when 

 deprived of its sympathetic nerves and this led him 



116. KiJHNE, Willy (1837- 1900). Uber die periphniuheii 

 Endorgane der molorisehrn .Herven. Leipzig: Engelmann, 

 1862. 



117. Kuhne, VV. On the oiigin and causation of vital move- 

 ment. Proc. Roy. Soc, London, ser. B 44: 427, 1888. 



118. Elliott, Thomas Renton (1877- ). On the action 

 of adrenaline. J. Physiol. 32: 401, 1905. 



119. Dale, Henry Hallett (1875- ). Transmission of 

 nervous effects of acetylcholine. Harvey Lectures 32: 229, 



'937- 



120. LoEVvi, Otto (1873- ). Uber humorale Ubertrag- 

 barkeit der Hcrtznervenwirkung. Arch. ges. Physinl. iBg- 

 23g, 1 92 1. 



