Stimulation rate modulates effects of the dihydropyridine CGP 28 392 on cardiac calcium-dependent action potentials.
Calcium (Ca2+)-dependent action potentials were recorded from 22 mM potassium (K+)-depolarized guinea-pig papillary muscle at several different pacing frequencies in the absence and presence of CGP 28 392 (10 microM), a Ca2+ channel agonist. The maximum upstroke velocity (Vmax) of the slow response action potential was measured to determine relative changes in Ca2+ current as a function of pacing frequency. CGP 28 392 increased Vmax more than two fold at low rates of stimulation (1 or 12 pulses min-1), but had no significant effect on Vmax during rapid pulsing (200 pulses min-1). The enhancement of Vmax was dependent upon extracellular [K+]. Increasing extracellular [K+] from 22 mM to 27 mM suppressed the frequency-dependent agonist effects and increased the antagonist effects on Vmax. These results indicate that CGP 28 392 is a partial Ca2+-channel agonist and suggest that its effects on Ca2+ current are voltage-dependent.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010210:Papillary Muscles / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D011725:Pyridines; C040525:CGP 28392; D009543:Nifedipine; D011188:Potassium; D002118:Calcium