Effect of Cleistanthus collinus leaf extract on neuromuscular function of the isolated mouse phrenic nerve-diaphragm

Cleistanthus collinus is a toxic plant whose leaves have been used for homicidal or suicidal purposes. Since the toxic effects include muscle cramps and weakness, the effect of the leaf extract on the electrical and mechanical responses to nerve and muscle stimulation was studied in the isolated phrenic nerve-diaphragm preparation of the mouse. Following a 1 hr exposure to 0.015% leaf extract, the response of the compound nerve action potential to supramaximal nerve stimulation was reduced by 38%. The compound muscle action potential was reduced by 97%, and isometric tension by 99%. In response to direct muscle stimulation the compound muscle action potential and isometric tension were reduced by 38%. There was only an 11% reduction in resting membrane potential, but a 51% reduction in the amplitude of miniature endplate potentials. Endplate potentials could be evoked by nerve stimulation without prior treatment of the muscle with curare or a high concentration of magnesium. These studies indicate that the leaf extract markedly inhibits muscle contraction by reducing excitability of the nerve and muscle membranes, and by blocking neuromuscular transmission, without affecting excitation-contraction coupling or contractility of the muscle fibers.