SKELETAL NEUROMUSCULAR TRANSMISSION 



207 



many of the characteristics of a response to a nerve 

 impulse. Their time course is similar to the endplate 

 potential in a curarized muscle. They appear largest 

 at the same place along the muscle fiber and become 

 attenuated by changes in the position of the recording 

 electrode in the same way. Furthermore, they are 

 diminished in amplitude by curare and increased 

 and prolonged by anticholinesterases. All the.se fea- 

 tures may be accounted for by the properties of the 

 postjunctional element and its reaction with acetyl- 

 choline. That the nerve terminals are responsible for 

 the release of acetylcholine producing these dis- 

 charges — called miniature endplate potentials — is 

 shown by the fact that they are abolished on nerve 

 degeneration and their frequency of occurrence is 

 modified by various treatments applied to the nerve. 

 In addition there is strong evidence that the end- 

 plate potential evoked by a nerve impulse is itself 

 resolvable into units of the size of miniature poten- 

 tials. 



The miniature discharges occur in a random time 

 sequence, the probability of occurrence in any given 

 inter\'al of time remaining constant irrespective of 

 previous discharges. The distribution of intervals be- 

 tween successive discharges is accordingly found to 

 follow a simple exponential function, decaying with 

 increasing interval, and can be descril)ed by a single 

 parameter, the mean frequency of discharge. E.xcep- 

 tions to this are occasional bursts which consist of a 

 number of miniature endplate potentials occurring 

 within a short period of time. They are the only indi- 

 cation of a possible coupling between discharges, and 

 can be readily recognized and excluded from a sta- 

 tistical analysis. In the frog under normal conditions 

 the mean frequency of spontaneous discharges varies 

 greatly at different junctions, extending at least over 

 the range o. i per sec. to 100 per .sec. In mammalian 

 muscle the frequency is more nearly constant around 

 I per sec. 



The distribution of amplitudes of the miniature 

 endplate potentials at a junction can be fitted ap- 

 proximately by a Gaussian curve with a standard 

 deviation equal to about 30 per cent of the mean. 

 With this relatively small variation, the amplitudes 

 effectively do not grade down to zero, and hence 

 under suitable recording conditions there is no un- 

 certainty in counting the discharges. By a variation in 

 recording technique, placing the microelectrode in 

 contact with the muscle fiber membrane without 

 penetrating it, it is possible to restrict the recording 

 of miniature discharges to those arising in a small 

 fraction of the junctional region contacted by the 



nerve terminals. In this way, one tenth or so of the 

 miniature discharges occurring within the fiber are 

 recorded selectively while the remainder appear 

 greatly attenuated and are in eflPect rejected (27). 

 Even under these conditions the amplitude of the 

 miniature potentials appears to be continuously 

 distributed, there being no clear indication of a 

 number of discrete .sizes which are repeated. 



A notable feature of the miniature discharge is 

 that the release of acetylcholine which produces it 

 does not appear to change under various treatments 

 which have an important influence on the genera- 

 tion of an electrical response (28). Even in the situa- 

 tion where the nerve and muscle membranes have 

 been completely depolarized i)y a high concentra- 

 tion of potassiimi ions, it can be shown by repolarizing 

 the muscle fiber with an applied current that the 

 intermittent release of sinall quantities of acetyl- 

 choline, capable of producing miniature potentials, 

 still occurs (26). It is therefore concluded that the 

 release of acetylcholine forming these discharges does 

 not depend upon the occurrence of electrical activity 

 of the action potential type in any structural unit 

 within the nerve terminal. 



Unlike the amplitude (considered as a quantity of 

 acetylcholine released from the terminal), the fre- 

 quency of the spontaneous discharges is highly sensi- 

 tive to changes in the condition of the preparation. 

 Changes in the osmotic pressure of the surrounding 

 fluid, for example, have a strong effect, the frequency 

 increasing reversibly as this is raised (41, 44, 62). A 

 finding which is important in indicating a possible re- 

 lation ijetween electrical events in the nerve and these 

 spontaneous discharges is that their frequency can 

 be altered by the application of a current to the 

 nerve which, by spreading into the terminal portion, 

 will alter the membrane polarization there (23, 64). 

 The frequency is found to vary approximately ex- 

 ponentially with changes in the polarizing current in 

 the nerve, being increased by depolarization of the 

 terminals. The frequency of discharge is also increased 

 when the concentration of potassium ions in the 

 bathing fluid is raised above the normal level, this 

 probably operating in the same way as current by- 

 causing a reduction of membrane potential. 



The rate of rise of the endplate potential, up to the 

 level at which an action potential is initiated, is 

 about one hundred times greater than the mean rate 

 of ri.se of the miniature endplate potential. A decrease 

 in the calcium ion concentration of the solution bath- 

 ing the preparation causes a reduction in the endplate 

 potential, while the amplitude of the spontaneous 



