608 Comparative Animcd Physiology 



CHEMICAL AGENTS IN NEUROMUSCULAR TRANSMISSION 



There are two hypotheses of neuromuscular transmission: one states that 

 a specific agent is liberated at nerve endings as a muscle excitant; the other 

 postulates that junctional transmission is electrical and that a chemical agent 

 is concerned equally with the electrical transmission in nerve and muscle. 



Activity in vertebrate parasympathetic nerves is associated with liberation 

 of acetylcholine (ACh) (Ch. 15, p. 537), at their terminations in heart 

 and blood vessels, and activity in most postganglionic sympathetic nerves to 

 these structures is associated with liberation of sympathin (possibly identical 

 with adrenin, Adr). In other animal groups the evidence for cholinergic 

 (acetylcholine-liberating) and adrenergic (adrenin-liberating) nerves to the 

 heart is not conclusive. There is presumptive evidence that various motor 

 nerves are cholinergic, adrenergic and tyraminic (liberating tyramine). The 

 distinction between cholinergic and adrenergic nerves is not rigorous, and 

 several types of interaction between ACh and Adr may exist (Ch. 23). 



Bacq^*'\ has stated criteria for identification of a chofinergic system: (1) 

 presence of ACh in- the tissue,* (2) presence of cholinesterase (ChE) 

 (acetylchohnesterase) in the tissue, (3) sensitivity to added ACh, (4) po- 

 tentiation of ACh and of nervous action by anticholinesterases such as ese- 

 rine, (5) blocking of action of ACh or nerve stimulation by atropine or 

 curare, and (6) identification of ACh in perfusate from the active organ. 

 Selected data for these criteria in neuromuscular preparations are given in 

 Table 73. 



The motor nerves in vertebrate striated muscle are cholinergic. Acetyl- 

 choline and acetylcholinesterase (ChE) are present: ChE is low in nerve- 

 free portions of muscle and is maximal in regions of end-plates. The con- 

 centration is higher in lizard muscle than in frog muscle,^^^ and in chickens 

 the ChE increases to a maximum at the time of hatching and thereafter de- 

 clines.^'^^ It has been calculated^'^^ that enough ChE is present in the frog 

 sartorius to spHt 1.6x10^ molecules of ACh at each end-plate during the 

 refractory period of the muscle. It is calculated that the output of acetyl- 

 choHne per nerve impulse per motor end-plate is 10""^° /u,g, or 1.4 X 10^ 

 molecules, which is 1/30,000 of that needed to stimulate.^ Immersion in 

 solutions of ACh causes a slow maintained contraction (contracture), and 

 some muscles, such as the frog rectus abdominis, are useful for bioassay 

 of ACh. Close intra-arterial injection of small amounts of ACh causes a 

 twitch-like response,**^- ^^ as do local ACh applications in the end-plate region. 

 The sensitivity to ACh is 1000 times greater at the end-plate than along the 

 fiber, possibly because of permeability differences.^ In perfusion experiments 

 ACh has been identified in increasing amounts in the perfusate when the 

 motor nerve to a muscle has been stimulated. Local applications of ACh, 

 like motor impulses, set up a local potential in the region of the end-plate, 

 and muscle impulses arise from this potential; eserine prolongs the e.p.p. 

 Eserine prolongs the summation interval for neuromuscular transmission, 

 and causes repeated contractions in response to a single motor volley, an effect 



* Acetylcholine is normally bound to protein in excitable tissues; free acetylcholine 

 appears to increase on stimulation and on standing in excised tissues. Determinations 

 of ACh are not always comparable in that they may not distinguish bound and free ACh. 



