Effects of pimobendan, a new cardiotonic agent, on contractile responses in single skeletal muscle fibres of the frog.
Effects of a new cardiotonic agent, pimobendan, on contraction were investigated in single intact skeletal muscle fibres of the frog. Pimobendan increased twitch tension in a concentration-dependent manner regardless of the presence or absence of Ca2+ without any effect on tetanic tension, the resting membrane potential and the shape of the action potential. Pimobendan caused a further increase in twitch tension potentiated by caffeine (1 mM). Adenine, an inhibitor of Ca2+-induced Ca2+ release from the sarcoplasmic reticulum, inhibited twitch tension potentiated by caffeine but not by pimobendan, suggesting that twitch potentiation by pimobendan is not attributed to increases in Ca2+-induced Ca2+ release. Pimobendan failed to increase cAMP levels in the skeletal muscle, though forskolin significantly increased it without any effect on twitch tension. Contractile responses to high concentrations of caffeine and K+ were also potentiated by pimobendan. These results suggest that the potentiating effect of pimobendan on skeletal muscle contraction is mainly due to the increase in Ca2+ sensitivity to the contractile apparatus.
Wakisaka
C
C
Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Kitamura
N
N
Ohta
T
T
Kai
T
T
Nakazato
Y
Y
Ito
S
S
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D011188:Potassium / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D014982:Xenopus laevis
D002316:Cardiotonic Agents; D011724:Pyridazines; C041648:pimobendan; D002110:Caffeine; D000242:Cyclic AMP; D011188:Potassium