JEAX BOTTS 87 



preparation (frog rectus abdominis muscle) exposed to varying concentrations 

 of ACh, suggest that 'activation' of each receptor molecule is achieved by 

 combination with exactly two ACh molecules (14). (Presumably these measure- 

 ments reflect the response of only the slow fiber component of this muscle; 

 refs. 14, 62.) 



The main effect of ACh at the end-plate is believed to be that of increasing 

 the membrane permeability to sodium ions, although a simultaneous increase in 

 permeability to potassium and possibly other ions also occurs. If sucrose is 

 substituted for NaCl in the external medium, ACh causes only a slight reduc- 

 tion in the end-plate potential, indicating that depolarization due to the influx 

 of the positively charged ACh itself is probably negligible (73). 



Since a single carrier molecule or unit makes possible the passage of several 

 thousand ACh molecules, an analogous amplification might be looked for im- 

 mediately at the end-plate in response to the ACh molecules. It has been esti- 

 mated that some io~^^ moles of ACh are released at an end-plate per nerve 

 impulse (2) and that more than 8 X io~'^ moles of monovalent ions flow across 

 the end-plate in the course of initiation of the propagated impulse in the muscle 

 fiber (22). These figures would correspond to the passage of about 10^ mono- 

 valent ions through the end-plate for each ACh molecule. (Such an estimate, 

 however, embodies several over-simplifications and may be regarded only as a 

 very rough first approximation.) 



Energy amplification at the neuromuscular junction is difficult to estimate. 

 But it seems clear that a large amplification occurs in the number of ions in- 

 volved, since the activation of a single ACh-carrier unit may result in the flow 

 of more than 10' ions through the end-plate. It is uncertain whether either of the 

 steps at the neuromuscular junction (ACh release and ACh action at the end- 

 plate) can be considered as triggered or triggering processes. The first of these 

 has been discussed above. Nachmansohn and Wilson (72) have postulated that 

 ACh can combine with a hypothetical receptor substance in nerve membrane 

 and produce a shape change in the receptor which allows a freer passage of ions. 

 If such a mechanism were operative at the end-plate, the action of ACh could 

 readily qualify as a triggering process. 



EVENTS AT THE MUSCLE FIBER MEMBRANE 



In the resting state of muscle the outside of the fiber membrane is positive 

 relative to the inside, the 'resting potential' being of the order of 85-95 millivolts 

 in frog muscle fibers (65, 74). The ratio of intracellular to extracellular electro- 

 lyte concentration is: about 40 or 50 for potassium, 1/6 for sodium, and 1/77 for 

 chloride (summarized, 36, 64). According to Boyle and Conway (7), if the resting 

 membrane is able to keep sodium ions out of the cell and is impermeable to 

 intracellular anions such as negatively charged protein molecules, a Donnan 

 distribution of the more permeable K+ and Cl~ is such as to account for a resting 



