FAILURE OF CHRONIC DENERVATION TO ALTER THE SENSITIVITY OF THE RAT DIAPHRAGM TO LOCAL ANAESTHETICS OR QUINIDINE

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Abstract
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.