Abstract

In the isolated diaphragm muscle of the rat, batrachotoxin (BTX) produced 1) a complete and irreversible block of the indirect and direct elicited muscle twitch; 2) an irreversible depolarization of the muscle membrane; and 3) the development of a muscle contracture having two temporally distinct phases. These effects of BTX were temperature dependent. The development of both BTX-induced membrane depolarization and muscle contracture was antagonized by tetrodotoxin. Lowering the extracellular sodium concentration or prior depolarization of the muscle membrane with Ringer's solution containing 100 mM K⁺ blocked the development of the first phase of BTX-induced muscle contracture. Raising the extracellular calcium concentration to 15 mM blocked the contracture-inducing effect of BTX whereas withdrawal of calcium allowed the first phase of BTX-induced contracture to occur earlier. Prior exposure of the diaphragm muscle to 10 mM [ethylenebis-(oxyethylenenitrilo)]-tetraacetic acid for one hour blocked the effect of caffeine and development of both phases of BTX-induced muscle contracture. After exposure of the diaphragm muscle to BTX for two hours at concentrations of 2.0 to 8.0 x 10^-3g/ml, potassium - and caffeine-induced muscle contractures were absent. Lower concentrations of BTX potentiated the initial response to caffeine and caused a reduction of the potassium contracture. It is concluded that both phases of BTX-induced muscle contracture are the result of depolarization mediated by a specific increase in sodium permeability. The selective disruption of the sarcoplasmic reticulum and terminal cisternae produced by BTX can account for the lack of caffeine-induced contracture.