Effects of cyclopiazonic acid on rat myocardium: inhibition of calcium uptake into sarcoplasmic reticulum.
The effects of cyclopiazonic acid (CPA), which is reported to inhibit Ca++ uptake into intracellular Ca++ store sites in skeletal and smooth muscles, were examined in ventricular myocardia of the adult rat. In isolated papillary muscle, 0.3 to 30 microM CPA concentration-dependently decreased the contractile force and prolonged the relaxation phase of twitch contractions. In skinned papillary muscle with functional sarcoplasmic reticulum (SR) preserved, application of CPA during the Ca++ loading period reduced the peak tension of subsequent caffeine-induced contractions. When CPA was applied during exposure to caffeine, it had no significant effect on the peak tension, but prolonged the decay of the caffeine-induced contraction. CPA had no substantial influence on the pCa-tension relationship of skinned fibers without functional SR. CPA had no substantial influence on the peak inward and steady-state membrane currents of isolated myocardial cells. These results suggest that CPA inhibits Ca uptake into SR by acting as a specific inhibitor of SR Ca(++)-ATPase in cardiac muscle as in skeletal and smooth muscles and thus provides a valuable pharmacological tool for studying myocardial excitation-contraction mechanisms.
Takahashi
S
S
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Kato
Y
Y
Adachi
M
M
Agata
N
N
Tanaka
H
H
Shigenobu
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004553:Electric Conductivity; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D007211:Indoles; D002118:Calcium; C000543:cyclopiazonic acid