Ca2+ handling in isolated human atrial myocardium

Physiologically, human atrial and ventricular myocardium are coupled by an identical beating rate and rhythm. However, contractile behavior in atrial myocardium may be different from that in ventricular myocardium, and little is known about intracellular Ca2+ handling in human atrium under physiolog ical conditions. We used rapid cooling contractures (RCCs) to assess sarcop lasmic reticulum (SR) Ca2+ content and the photoprotein aequorin to assess intracellular Ca2+ transients in atrial and ventricular muscle strips isola ted from nonfailing human hearts. In atrial myocardium (n = 19), isometric twitch force frequency dependently (0.25-3 Hz) increased by 78 +/- 25% (at 3 Hz; P < 0.05). In parallel, aequorin light signals increased by 111 +/- 5 7% ( P < 0.05) and RCC amplitudes by 49 +/- 13% (P < 0.05). Similar results were obtained in ventricular myocardium (n = 13). SR Ca2+ uptake (relative to Na+/Ca2+ exchange) frequency dependently increased in atrial and ventri cular myocardium (P < 0.05). With increasing rest intervals (1-240 s), atri al myocardium (n = 7) exhibited a parallel decrease in postrest twitch forc e (at 240 s by 68 +/- 5%, P < 0.05) and RCCs (by 49 +/- 10%, P < 0.05). In contrast, postrest twitch force and RCCs significantly increased in ventric ular myocardium (n = 6). We conclude that in human atrial and ventricular m yocardium the positive force-frequency relation results from increased SR C a2+ turnover. In contrast, rest intervals in atrial myocardium are associat ed with depressed contractility and intracellular Ca2+ handling, which may be due to rest-dependent SR Ca2+ loss (Ca2+ leak) and subsequent Ca2+ extru sion via Na+/Ca2+ exchange. Therefore, the influence of rate and rhythm on mechanical performance is not uniform in atrial and ventricular myocardium.