Abstract

To elucidate the mechanisms of the negative inotropism induced by excessive intracellular Ca2+ ([Ca2+]i), we observed detailed characteristics of twitch contractions during low Na+-induced [Ca2+]i overload. Rat right ventricular trabecular muscles were superfused with a low-Na+ solution ([Na+]o:50, 25, 18, and 14 mM), obtained by substituting choline-Cl for NaCl at 30 degrees C on the stage of an inverted microscope and electrically stimulated at the rate of 12 pulses/min (n = 6). Each low-Na+ perfusion decreased developed tension with the increase in resting tension (Ca2+ overload). As [Na+]o decreased below 50 mM, peak contracture tension increased and developed tension at peak contracture decreased. The decrease in developed tension coincided with the appearance of the marked aftercontractions and with the increase in fluctuating intracellular contractile activities during the resting period, which have been ascribed to [Ca2+]i oscillations. Neither maximum rate of tension development nor minimum rate of relaxation showed significant changes during the phase of Ca2+ overload. These results suggest that the decrease in developed tension during Ca2+ overload is due to [Ca2+]i oscillations, rather than due to depressed contractility and relaxation.

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