ABNORMAL CAI2+ HANDLING IS THE PRIMARY CAUSE OF MECHANICAL ALTERNANS - STUDY IN FERRET VENTRICULAR MUSCLES

We tested the hypothesis that mechanical alternans of the heart is due to alterations in intracellular calcium (Ca(i)2+) levels. Eight papillary muscles were isolated from the right ventricles of male ferrets and were chemically loaded with aequorin to record cytoplasmic Ca(i)2+. 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 (Ca(i)2+) 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 Ca(i)2+ 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 Ca(i)2+ 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 Ca(i)2+ handling during mechanical alternans.