Enhancement of spontaneous acetylcholine release from motor nerve terminal by calmodulin inhibitors.
The role of calmodulin (CaM) in neuromuscular transmission in the rat diaphragm was electrophysiologically investigated using a microelectrode technique with two different CaM inhibitors, trifluoperazine (TFP) and N-(6-aminohexyl)-5-chrolo-1-naphthalene-sulfonamide HC1 (W-7). These inhibitors in the perfusate decreased the amplitude of miniature endplate potentials and increased the frequency dose dependently without any changes occurring in the resting membrane potentials. These effects were abolished in a Ca2+-free perfusate. The acetylcholine (ACh) quantal size and content were not affected by the reagents. The effects of TFP and W-7 were thought to result from their specific inhibition of calmodulin. It is suggested that accumulated intracellular Ca2+ and cyclic AMP, due to inhibition of calmodulin, had enhanced the frequency of spontaneous ACh release from the nerve terminal, and the decrease in the amplitude might be attributed to inhibition of the postsynaptic action of CaM.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D013449:Sulfonamides; D014268:Trifluoperazine; C017967:W 7; D000109:Acetylcholine