Biphasic inotropic effects of a Ca2+ channel activator CGP28392 in rat myocardium: possible relation to intracellular Ca2+ release.
1. The inotropic effect of a Ca2+-entry stimulator, CGP28392, (CGP) was compared in rat and frog myocardium in a concentration- and time-dependent manner. 2. Frog preparations exhibited a persistent positive inotropic effect following prolonged treatment with CGP. 3. Compared to amphibian myocardium, rat ventricular muscle exhibited a biphasic time-dependent response to CGP: an initial increase in the twitch tension amplitude of 30% was changed to a reduction of 80% below the control level during prolonged exposure to CGP (stimulation frequency, 0.2 Hz). 4. Following prolonged incubation with CGP, the resting-state contraction was decreased and the negative force-frequency relation was converted into a positive one in rat muscle. 5. Since sarcoplasmic reticulum (SR) is the major source of Ca2+ in a rested-state contraction, inhibition by CGP suggests an additional, intracellular action of the Ca2+ channel activator on SR-Ca2+ release in rat myocardium.
Institute of Biological Physics, Acad. Sci. of the USSR, Pushchino.
E
E
Kobrinsky
M
M
Saxon
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D011895:Rana ridibunda; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002120:Calcium Channel Agonists; D011725:Pyridines; C040525:CGP 28392; D002118:Calcium