Effects of [Na+]o, [Ca2+]o and cyclopiazonic acid on decline of post-extrasystolic potentiation and twitch kinetics in guinea-pig and human myocardial preparations.
The decline of post-extrasystolic potentiation was investigated in atrial and ventricular muscle of guinea-pigs and in human atrial muscle. This decline is described in terms of the recirculation fraction (RF) for calcium in myocardial cells. Under control conditions, the mean values for RF were as follows: 0.61 +/- 0.03 in the guinea-pig atrium, 0.32 +/- 0.05 in the guinea-pig ventricle and 0.51 +/- 0.10 in the human atrium. Upon increasing calcium concentrations within the range of 0.5-10 mM or decreasing the sodium to 70%, the steady-state force and recirculation fraction increased concomitantly in all three types of muscles. Cyclopiazonic acid (CPA), in a 5-20 microM concentration, decreased force in the guinea-pig preparations and decreased RF. The effects of CPA were great in atrial muscle, 20 microM CPA decreasing RF from 0.61 to 0. 39. In ventricular muscle, this effect was small and not statistically significant. When changing calcium or sodium concentrations, increased force was accompanied by slower relaxation in atrial muscle, but an unchanged or slightly faster relaxation in ventricular muscle. In guinea-pig myocardium, CPA (5-20 microM) prolonged the time to peak force (TPF), but it slowed relaxation only in the ventricle. Reducing the calcium outflow by Na/Ca exchange increased RF as expected, and reducing the SR calcium re-uptake decreased RF. These interventions were also expected to reduce the rate of decline of intracellular calcium, but relaxation was not consistently prolonged. This indicates that factors other than the SR calcium pump and sarcolemmal Na/Ca exchange determine, or at least influence, the rate of relaxation.
Asgrimsson
H J
HJ
Department of Pharmacology, University of Iceland, Reykjavik, Iceland.
Wohlfart
B
B
Brandt
J
J
Jóhannsson
M
M
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D007211:Indoles; D012964:Sodium; D002118:Calcium; C000543:cyclopiazonic acid