BAY K 8644 and ClO4- potentiate caffeine contracture without Ca2+ release channel activation.
Effects of perchlorate (ClO4-) and BAY K 8644 on caffeine contracture and Ca2+ release channel current were studied in frog skeletal muscle. Single fibers produced a small transient contracture on addition of 2.2 mM caffeine. ClO4 at 10 mM enhanced caffeine contracture 3.7-fold. This effect was inhibited by 10 microM nifedipine pretreatment. An increase in caffeine contracture was also obtained after exposure to 0.1 microM BAY K 8644 for 1 h. At 20 mM, external K+ potentiated caffeine contracture 2.2-fold. ClO4- (< 10 mM) and BAY K 8644 (0.1-1 microM) did not affect open probability (Po), unitary conductance, and open and closed time constants of the Ca2+ release channel current. BAY K 8644 at 0.1 microM did not further enhance the channel that had been activated by 2 mM caffeine. However, 20-30 mM ClO4 increased Po significantly and led the channel to a long open state by increasing the slow open time constant and decreasing the fast closed time constant. These results suggest that binding of ClO4 and BAY K 8644 to dihydropyridine receptors elicits a further increase in Ca2+ release from the sarcoplasmic reticulum.
Oba
T
T
Department of Physiology, Nagoya City University Medical School, Japan.
Koshita
M
M
Aoki
T
T
Yamaguchi
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D004357:Drug Synergism; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010472:Perchlorates / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011892:Rana catesbeiana; D017670:Sodium Compounds / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010472:Perchlorates; D017670:Sodium Compounds; D002110:Caffeine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C031068:sodium perchlorate; D009543:Nifedipine; D011188:Potassium