The relationship between stimulus-induced antidromic firing and twitch potentiation produced by paraoxon in rat phrenic nerve-diaphragm preparations

Abstract

The relationship between stimulus-induced repetitive antidromic firing (ADF) in the motor nerve and twitch potentiation produced by the organophosphate anticholinesterase paraoxon, has been investigated in rat diaphragm preparations. Little or no ADF was produced by paraoxon in preparations bathed in a Tyrode solution containing 1 mM calcium and 1 mM magnesium ions although the preparations showed marked twitch potentiation. Increases in the calcium:magnesium ion ratio produced a ratio-dependent increase in the ADF but had no consistent effect on peak twitch potentiation. Dithiothreitol, a disulphide bond reducing agent which decreases the affinity of acetylcholine for nicotinic cholinoceptors, abolished ADF but only modified the time course of twitch potentiation. Dithiothreitol, a disulphide bond reducing agent which decreases the affinity of acetylcholine for nicotinic cholinoceptors, abolished ADF but only modified the time course of twitch potentiation. It is concluded that the initiation of ADF is a consequence of the prolonged action of acetylcholine within the synaptic cleft following inhibition of acetylcholinesterase, and that ADF is not the only mechanism by which twitch potentiation can be produced.