Failure of chronic denervation to alter the sensitivity of the rat diaphragm to local anaesthetics of quinidine.

1 The actions of procaine, nupercaine and quinidine on the membrane resting and action potentials of the normal and chronically denervated rat diaphragm were studied in vitro.2 The degree of suppression of the rate of rise of the action potential by any of the drugs was the same in denervated as in normal muscle.3 The degree of suppression of the rate of rise of the action potential by procaine in denervated muscle was about the same in the presence and absence of tetrodotoxin.4 Three possible interpretations of the lack of effect of denervation on the response to these drugs are discussed:(a) In the sodium channel, the structural alteration that confers resistance to tetrodotoxin is quite limited and does not affect groups which interact with local anaesthetics.(b) Local anaesthetics are non-selective in their binding so that alteration in membrane structure around the channel has little influence on the efficiency of the local anaesthetic.(c) Denervation may affect the outer surface of the membrane, where acetylcholine and tetrodotoxin act, more than the intracellular surface, where local anaesthetics appear to act.5 The slope of the log concentration-effect line for quinidine was steeper than that for procaine or nupercaine.