Action Potential Prolongation in Cardiac Myocytes of Old Rats is an Adaptation to Sustain Youthful Intracellular Ca2+ Regulation

Autor: Harold A. Spurgeon, Edward G. Lakatta, Andrzej M. Janczewski
Rok vydání: 2002
Předmět:
Zdroj: Journal of Molecular and Cellular Cardiology. 34:641-648
ISSN: 0022-2828
Popis: A. M. Janczewski, H. A. Spurgeon and E. G. Lakatta. Action Potential Prolongation in Cardiac Myocytes of Old Rats is an Adaptation to Sustain Youthful Intracellular Ca2+ Regulation. Journal of Molecular and Cellular Cardiology (2002) 34, 641–648. Advanced age in rats is accompanied by reduced expression of the sarcoplasmic reticulum (SR) Ca2+ pump (SERCA-2). The amplitudes of intracellular Ca2+ (Ca2+i) transients and contractions in ventricular myocytes isolated from old (23–24-months) rats (OR), however, are similar to those of young (4–6-months) rat myocytes (YR). OR myocytes also manifest slowed inactivation of L-type Ca2+ current (ICaL) and marked prolongation of action potential (AP) duration. To determine whether and how age-associated AP prolongation preserves the Ca2+i transient amplitude in OR myocytes, we employed an AP-clamp technique with simultaneous measurements of ICaL (with Na+ current, K+ currents and Ca2+ influx via sarcolemmal Na+-Ca2+ exchanger blocked) and Ca2+i transients in OR rat ventricular myocytes dialyzed with the fluorescent Ca2+ probe, indo-1. Myocytes were stimulated with AP-shaped voltage clamp waveforms approximating the configuration of prolonged, i.e. the native, AP of OR cells (AP-L), or with short AP waveforms (AP-S), typical of YR myocytes. Changes in SR Ca2+ load were assessed by rapid, complete SR Ca2+ depletions with caffeine. As expected, during stimulation with AP-S vs AP-L, peak ICaL increased, by 21±4%, while the ICaL integral decreased, by 19±3% (P
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