Effects of nifedipine and Bay K 8644 on contractile activities in single skeletal muscle fibers of the frog.
The effects of dihydropyridine derivatives on contractile activity were examined in single fibers of frog skeletal muscles. Both nifedipine and Bay K 8644 enhanced twitch responses regardless of the presence or absence of Ca2+ without any effects on the resting membrane potential, evoked action potential and Ca2+ sensitivity of the contractile machinery. Twitch responses enhanced by Bay K 8644, but not by nifedipine, were partially reduced by adenine, an inhibitor of Ca(2+)-induced Ca2+ release from sarcoplasmic reticulum, suggesting the involvement of Ca(2+)-induced Ca2+ release in Bay K 8644-induced potentiation of the twitches. Both nifedipine and Bay K 8644 caused a dose-dependent potentiation of K+ contractures without any effects on the membrane potential in the presence of Ca2+, but inhibited the contractures in the absence of Ca2+. These results suggest that dihydropyridine derivatives modify contractile activities of skeletal muscles by modulating the dihydropyridine receptors on the surface of T-tubules acting as voltage sensors.
Kitamura
N
N
Department of Pharmacology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Ohta
T
T
Ito
S
S
Nakazato
Y
Y
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000225:Adenine / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D066298:In Vitro Techniques; D008839:Microelectrodes; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000166:cytology / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D014982:Xenopus laevis
D004095:Dihydropyridines; D002110:Caffeine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D000225:Adenine; D011188:Potassium; D002118:Calcium