AJP - Heart and Circulatory Physiology, Vol 261, Issue 6 1746-H1755, Copyright © 1991 by American Physiological Society

ARTICLES

Abnormal Cai2+ handling is the primary cause of mechanical alternans: study in ferret ventricular muscles

Y. Kihara and J. P. Morgan
Second Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.

We tested the hypothesis that mechanical alternans of the heart is due to alternations in intracellular calcium (Cai2+) levels. Eight papillary muscles were isolated from the right ventricles of male ferrets and were chemically loaded with aequorin to record cytoplasmic Cai2+. To produce a steady-state mechanical alternans, the preparations were perfused with a physiological salt solution containing a low calcium concentration (0.25 mM), at 22 degrees C, and stimulated at 0.5-1.0 Hz in the presence of carbachol and propranolol. The aequorin signal (Cai2+) and isometric contraction were simultaneously recorded. In each muscle, the strong beats (beats with higher peak tension) were associated with larger Ca2+ transients than the weak beats. The relationships between peak Cai2+ and peak tension, both during strong and weak beats, were similarly modified by short-term frequency responses. On the other hand, the time courses of the isometric contractions and Ca2+ transients during strong beats and weak beats were superimposable. These data indicate that mechanical alternans is caused by an alternate change of Cai2+ available for activation of the myofilaments. Prolongation of the time for recycling Ca2+ by the sarcoplasmic reticulum, i.e., a depressed uptake function of the Ca2+ pump with concomitant slow transportation of Ca2+ from the uptake compartment to the release compartment in the sarcoplasmic reticulum, is suggested as a cause of the abnormal Cai2+ handling during mechanical alternans.

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