Postsynaptic inhibition of neuromuscular transmission by trifluoperazine.
The effect of trifluoperazine (TFP) on neuromuscular transmission was investigated on chick biventer cervicis and frog cutaneous pectoris and sartorius nerve-muscles. In the chick, TFP inhibited indirectly elicited twitches in a frequency-dependent manner. Inhibition was much more rapid at higher frequencies of stimulation. Directly elicited twitches, KCl contracture and action potentials of desheathed frog sciatic nerve and sartorius muscles were unaffected by TFP, suggesting an action of TFP on neuromuscular transmission. TFP depressed end plate potential amplitude and miniature end plate potential (MEPP) amplitude without affecting MEPP frequency. When MEPP frequency was increased by high Na+ Ringer, depression of MEPP amplitude was much more rapid. Similarly, at high frequencies of stimulation (100 Hz), TFP rapidly depressed end plate currents. TFP inhibited contractures induced by bath-applied acetylcholine (ACh); depressed ACh potentials produced by iontophoretically applied ACh; decreased ionic current and time constant of decay of end-plate currents of transected muscle; and inhibited [alpha-125I]bungarotoxin binding to ACh receptor. These data suggest that TFP acts postsynaptically in a frequency-dependent manner to inhibit neuromuscular transmission. Based on recent evidence that TFP is a potent antagonist of calmodulin and that calmodulin is localized mainly to postsynaptic regions, we postulate that the postsynaptic inhibitory actions of TFP may be mediated through antagonism of calmodulin, which in turn may regulate ACh receptor function.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D001001:Anura; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002645:Chickens; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D014268:Trifluoperazine / Q000494:pharmacology*
D002147:Calmodulin; D014268:Trifluoperazine; D000109:Acetylcholine