The actions of eserine-like compounds upon frog’s nerve-muscle preparations, and conditions in which a single shock can evoke an augmented muscular response

Abstract

The muscular responses to one shock, or two shocks separated by 3-10 msec., applied to the nerve of a frog's nerve-sartorius preparation, when immersed in Ringer's solution containing glucose and buffered with bicarbonate, were reasonably constant for about 3 hr. The main response to two shocks was followed by a small after-tension, which, like Bremer's (1932) 'neuromuscular contracture', was abolished by atropine in concentration too small to influence the main response, or by curarine in concentrations which somewhat reduced the main response. Treating nerve-sartorius preparations from frogs which had been kept at 14-18°C for some days before use ('warm' frogs) with prostigmine, eserine, or the dimethylcarbamic ester of 8-hydroxymethylquinolinium methylsulphate, usually produced no change in the main response to one or to two shocks, but augmented the after-tension in the response to two shocks, and caused an after-tension to follow the response to a single shock. On the other hand, treating preparations from frogs which had been kept at 0-5°C for more than 40 hr. before use ('cold' frogs) with any of the eserine-like compounds caused the response to one or to two shocks to become augmented, as with mammalian preparations, and to be followed by irregular twitchings which lasted for about a second. The after-twitchings were abolished by atropine in concentrations which slightly reduced the main response, or by curarine in concentrations which reduced the main response rather more. Treating 'warm' preparations with Ringer's solution of half the usual calcium content, or with Ringer's solution containing any of the following agents (which are known to sensitize to stimuli of long duration), in small concentration, produced no appreciable change in the responses: tetraethylammonium iodide, sodium citrate, guanidine carbonate, or methyl-guanidine hydrochloride. If, however, preparations so treated were also treated with any of the eserine-like compounds, their responses then became like those of a 'cold' preparation which had been treated with an eserine-like compound. The responses evoked by applying one shock, or two with an interval of 3-10 msec. between them, to the pelvic end of the frog's sartorius muscle, after sufficient curarine to render nerve stimulation ineffective, were uninfluenced by any of the eserine-like compounds, or by any of the five agents mentioned in the previous paragraph, provided that shocks of short duration were used: when condenser discharges of long duration were used, treatment of 'warm' preparations with any of the five agents, in the same concentrations as produced the changes described in the previous paragraph, augmented the response. Calcium-deficiency, in large or small degree, affected little the response to stimulation of muscle. But a moderate deficiency changed the responses to repetitive stimulation of nerve in such a way as might have been imitated by stimulating the nerve of the untreated preparation at a lower frequency. When the deficiency was more severe, on stimulating with 150 shocks per sec., no response was visible for the first 1-3 sec., the tension then rose to less than a quarter of its normal maximum, and afterwards fell slowly. Prostigmine in large concentrations produced little improvement, whereas calcium quickly produced a marked improvement.