Effects of chlorhexidine on the isolated rat phrenic nerve-diaphragm preparation

Dose-dependent inhibitory effect of chlorhexidine (2.5 x 10(-5)-5.0 x 10(-4) g/ml on neuromuscular transmission were localized by tension and electromyogram recording during indirect stimulation. Subsequent direct stimulation showed an additional inhibition which might be located to the sarcolemma. In addition, contracture was observed at the highest concentrations. Microelectrode experiments showed a miniature endplate potential frequency increase (at 1.0 x 10(-6) g/ml), suggesting a presynaptic action. Increasing the dose to 5.0 x 10(-6) g/ml disclosed a decrease of the miniature endplate potential amplitude, indicating a reduction of the postsynaptic receptor sensitivity, which might cause neuromuscular inhibition. This was confirmed by endplate potential recording in cut preparations. The endplate potential showed a moderate degree of use-dependent inhibition which did not usually cause a tetanic fade. Experiments with curare, decamethonium and neostigmine indicated that chlorhexidine probably caused a decamethonium-like inhibition. A small depolarization of the sarcolemma was probably not the cause of the directly elicited inhibition or contracture. The contracture was potentiated in preparations made myotonic by pretreatment with para-hydroxy-mercuribenzoate. It could not be inhibited by the excitation-contraction uncoupler dantrolene, but it was dependent on extracellular Ca2+. Chlorhexidine-induced influx of Ca2+ might thus cause the contracture.