ECCLES: ELECTRICAL THEORIES OF TRANSMISSION 431 



cells to discharge. The usual transmission mechanism was due to an 

 excitatory action, unaffected by eserine and brief enough to be at- 

 tributable to the action currents of the pre-ganglionic impulses. ^^' '^ 



(ii) A similar study of synaptic potentials of motoneurones excited 

 through mono-synaptic reflex pathways of the spinal cord (frog, cat) 

 has failed to detect even such a subsidiary role for acetylcholine trans- 

 mission.^^ Furthermore, it has been found that synaptic transmission 

 of the frog's spinal cord is unaffected by prolonged soaking (several 

 hours) in high concentrations of acetylcholine (up to 1 in 5,000) . Still 

 higher concentrations have an anesthetic action which, initially, is 

 reversible. The isolated oxygenated cord (anesthetized or unanes- 

 thetized) is soaked for 30 min. in a strong anti-cholinesterase (1 in 

 50,000 eserine), and then the acetylcholine is added to the solution." 

 These experiments would appear to falsify the hypothesis that acetyl- 

 choline plays a major role in synaptic transmission in the spinal cord. 

 However, too much emphasis should not be placed on these latter ex- 

 periments, until they are repeated with prostigraine as an anti-cholin- 

 esterase (cf. iii, below). 



(iii) Just as with sympathetic ganglia,^'' the responses of curarized, 

 eserinized (or prostigminized) muscles to repetitive stimulation are 

 sharply distinguishable into a prolonged end-plate potential which is 

 attributable to acetylcholine, and an initial, very brief, end-plate 

 potential, but little lengthened by anti-cholinesterases.^^' ^'^ It seems 

 probable that, as with ganglia, the small, apparent lengthening of the 

 initial phase by anti-cholinesterases may be attributable to some ad- 

 mixture of the prolonged acetylcholine phase, and that the initial phase 

 may be excited by the action currents of pre-synaptic impulses (cf. 

 PART 8, ii). Acetylcholine blocks neuro-muscular transmission,^' ^ pre- 

 sumably by catelectrotonic blockage, but, despite a relatively high 

 acetylcholine background (1 in 200,000), pre-synaptic volleys still set 

 up large end-plate potentials, even larger than in curarized muscle.^® 

 When performing these experiments by soaking frog's sartorii in acetyl- 

 choline solutions, prostigmine is used as an anti-cholinesterase. Eser- 

 ine is ineffective, probably because acetylcholine competes with it for 

 the cholinesterase."* 



3. EXPERIMENTAL BASIS FOR ELECTRICAL HYPOTHESIS 



In recent years, important advances have been made in the investiga- 

 tion of nerve and muscle fibers, and an electrical hypothesis of trans- 

 mission must be based on the following evidence: 



* Cf. Eccles, J. C, B. Katz, 8c S. W. Kufller.^^: 225. 



