DIFFERENTIAL EFFECT OF PERHYDROHISTRIONICOTOXIN ON INTRINSIC AND EXTRINSIC ENDPLATE RESPONSES

1. At rat and frog neuromuscular junctions, perhydrohistrionicotoxin (H12‐HTX), at concentrations below 10(‐6) M, blocked end‐plate currents and potentials generated by ionophoretic application of ACh (extrinsic responses) more effectively than end‐plate currents and potentials generated by neurotransmitter secreted from the motor nerve (intrinsic responses). 2. In contrast, (+)‐tubocurarine affected both extrinsic and intrinsic responses in a parallel manner. 3. There was no change in the time course and little or no change in the amplitude of intrinsic end‐plate currents when extrinsic currents were depressed by H12‐HTX nor was there any change in the conductance or lifetime of channels activated by applied ACh. 4. The depressant effect of H12‐HTX on extrinsic responses persisted both when carbachol was used as the agonist and when acetylcholinesterase was inhibited with diisopropylfluorophosphate. 5. Large end‐plate currents elicited by nerve stimulation that presumably activate the whole end‐plate area were not depressed by H12‐HTX to the same degree as extrinsic end‐plate currents generated by ionophoresis of ACh at the same end‐plate. 6. Brief (50 microsec) pulses of ACh produced brief end‐plate potentials which were depressed by concentrations of H12‐HTX that had little or no effect on miniature end‐plate potentials. 7. Extrinsic responses to ACh at extrajunctional regions of denervated fibres were also depressed by low concentrations of H12‐HTX. 8. It was concluded that the differential effects of H12‐HTX on intrinsic and extrinsic end‐plate responses could be due to the existence of two populations of receptor‐channel complexes or to protection of local receptor‐channel complexes from the toxin by a substance secreted from motor nerve terminals. © 1979 The Physiological Society