Dihydropyridine-sensitive and -insensitive components of acetylcholine release from rat motor nerve terminals.
Effects of the dihydropyridine (DHP) calcium channel agonist Bay K 8644 on spontaneous and neurally evoked release of acetylcholine were measured using conventional intracellular microelectrode recording techniques at rat neuromuscular junctions of preparations that were transected to prevent contraction ("cut muscle preparation"). At concentrations of 0.65 to 2 microM Bay K 8644 caused significant increases in end-plate potential amplitude and mean quantal content in cut muscle preparations, but no effect in uncut preparations in which contractions were blocked by using d-tubocurarine (1 microM). The dose-dependence of this effect occurred over a very narrow concentration range. This increase in quantal content, which occurred within 5 to 10 min of application of Bay K 8644, could be blocked by pretreatment or reversed by subsequent treatment of the preparation with nimodipine, a DHP antagonist. Nimodipine itself had no effect on quantal content. At concentrations of Bay K 8644 in excess of 1 microM, increase quantal content was usually followed by a subsequent complete failure of nerve-evoked release of transmitter. Administration of Bay K 8644 was also associated with an increase in the frequency of miniature end-plate potentials (MEPPs). This effect was observed in 5 of 6 "cut" and only 1 of 6 "uncut" preparations. Increase of MEPP frequency occurred after a latent period of 15 to 25 min of treatment with Bay K 8644, and was not prevented pretreatment with nimodipine. Nimodipine itself had no effect on MEPP frequency. Increased MEPP frequency occurred in cut preparations treated with Bay K 8644, but with solutions to which no extracellular Ca++ was added.(ABSTRACT TRUNCATED AT 250 WORDS)
Atchison
W D
WD
Department of Pharmacology and Toxicology Michigan State University, East Lansing.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009045:Motor Endplate / Q000187:drug effects* / Q000502:physiology; D009469:Neuromuscular Junction; D051381:Rats; D011919:Rats, Inbred Strains; D015222:Sodium Channels / Q000187:drug effects
D002121:Calcium Channel Blockers; D015222:Sodium Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000109:Acetylcholine; D002118:Calcium