Ca²⁺ handling in isolated human atrial myocardium

Abstract

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 Ca(2+) handling in human atrium under physiological conditions. We used rapid cooling contractures (RCCs) to assess sarcoplasmic reticulum (SR) Ca(2+) content and the photoprotein aequorin to assess intracellular Ca(2+) transients in atrial and ventricular muscle strips isolated 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 +/- 57% (P < 0.05) and RCC amplitudes by 49 +/- 13% (P < 0.05). Similar results were obtained in ventricular myocardium (n = 13). SR Ca(2+) uptake (relative to Na(+)/Ca(2+) exchange) frequency dependently increased in atrial and ventricular myocardium (P < 0.05). With increasing rest intervals (1-240 s), atrial myocardium (n = 7) exhibited a parallel decrease in postrest twitch force (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 ventricular myocardium (n = 6). We conclude that in human atrial and ventricular myocardium the positive force-frequency relation results from increased SR Ca(2+) turnover. In contrast, rest intervals in atrial myocardium are associated with depressed contractility and intracellular Ca(2+) handling, which may be due to rest-dependent SR Ca(2+) loss (Ca(2+) leak) and subsequent Ca(2+) extrusion via Na(+)/Ca(2+) exchange. Therefore, the influence of rate and rhythm on mechanical performance is not uniform in atrial and ventricular myocardium.

Active stiffening of mitral valve leaflets in the beating heart

“…Previous studies demonstrated that anterior leaflet cardiac muscle is excited with each atrial systole (7,33) and, similar to atrial myocardium (25), contracts for only ϳ200 ms after the onset of ventricular systole (32). In isolated tissue, excitation propagates from the LA into the anterior leaflet (12,48) but spreads more slowly in the leaflet (40 -60 ms) than in the atrium (6 -10 ms) (12), with force developed for ϳ200 ms, at most, after transmembrane depolarization of leaflet cardiac muscle (12).…”

“…Ecirc ( ulation (12,39) via propagated depolarization [35-ms stimulus latency, 210-ms refractory period, 6% shortening (39)] and exhibit a positive inotropic response to norepinephrine and tyramine and a negative inotropic response to stimulus frequency (25,39) and acetylcholine (reversible with atropine) (12,39).…”

Difference in Propagation of Ca2+ Release in Atrial and Ventricular Myocytes

“…It has been previously reported that contraction and relaxation processes are faster in atrial than in ventricular myocardium [24][25][26][27][28], but the underlying mechanisms are unclear. Rat atrial myocytes have about twofold greater SR Ca 2+ -ATPase protein relative to ventricular myocytes [27].…”

Effect of inhibitors of mitochondrial respiratory chain complexes on the electromechanical activity in human myocardium

“…About 80% to 90% of cellular ATP is produced by mitochondrial oxidative phosphorylation; the most part of generated ATP (>60%) is consumed for the con traction-relaxation of myocardium (5). Mitochondrial F 1 F 0 -ATP synthase uses the proton gradient, generated by complexes I, III, and IV of the electron transport chain, to generate ATP from ADP.…”