Differential effect of perhydrohistrionicotoxin on 'intrinsic' and 'extrinsic' end-plate 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.
D000109:Acetylcholine / Q000494:pharmacology; D000664:Amphibian Venoms / Q000494:pharmacology*; D000818:Animals; D001001:Anura; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D005260:Female; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology*; D011894:Rana pipiens; D051381:Rats; D014403:Tubocurarine / Q000494:pharmacology
D000664:Amphibian Venoms; C004792:perhydrohistrionicotoxin; D000109:Acetylcholine; D014403:Tubocurarine