AN ELECTRICAL HYPOTHESIS OF SYNAPTIC 

 AND NEURO-MUSCULAR TRANSMISSION 



By J. C. EccLES 



University of Otago, Dunedin, New Zealand 



1. PRESENT THEORETICAL POSITION 



This paper will be restricted to the synapses of ganglia and the spinal 

 cord and to the neuro-muscular junctions of skeletal muscle (hence- 

 forth, collectively referred to as synapses), because, physiologically, 

 they form a fairly homogeneous group. A preliminary report has al- 

 ready been published.^* There is now good evidence that the trans- 

 mission of impulses, at all these synapses, is mediated by catelectrotonic 

 potentials set up at the synaptic membrane of the post-synaptic cell — 

 the end-plate potentials of skeletal muscle-^' ^^' ^*' ^^' ^°' " and the 

 synaptic potentials of ganglion cells^"' ^^ and motoneurones.^' ^^' ^^ We 

 may, therefore, subdivide the problem of synaptic transmission into 

 two Problems: (a) the mechanism whereby impulses in pre-synaptic 

 nerve fibers set up catelectrotonic synaptic potentials in the post- 

 synaptic cell; and (b) the initiation of impulses in the post-synaptic 

 cell by these synaptic potentials. As is well known, the existing hy- 

 potheses relating to Problem (a) are chemical (acetylcholine), or elec- 

 trical, or some combination thereof.*' -''' *^^ Problem (b) has, hitherto, 

 been regarded as just a part of the general problem of impulse initiation 

 by catelectrotonus. However, there is evidence of a unique mechanism 

 in the case of the only synapse worked on in detail.^" 



There is some resemblance between these two stages of synaptic 

 transmission and the two "boundary faces" postulated by Buchthal and 

 Lindhard,^' ^ to explain the two stages of neuro-muscular block pro- 

 duced by curare and acetylcholine. 



In their existing form, both hypotheses relating to Problem (a) are 

 unsatisfactory : 



(i) Originally, the acetylcholine hypothesis simply stated that a pre- 

 synaptic impulse liberated at the synapse a sudden jet of acetylcholine, 

 which excited the post-synaptic cell by acting on specific receptors ;^^ 

 thus set up the synaptic potential, according to present views; and 

 was ickly removed by the locally concentrated cholinesterase.®- ^' "• ^^ 

 The usual failure to detect acetylcholine in venous blood collected from 



(429) 



