INTRACELLULAR CALCIUM TRANSIENTS IN POTENTIATED CONTRACTIONS INDUCED BY MULTIPLE EXTRASYSTOLIC BEATS IN ISOLATED-PERFUSED RAT HEARTS

Mechanisms underlying contractile potentiation induced by multiple ext rasystolic contractions (ESC) were evaluated with surface fluorometry in isolated perfused rat hearts loaded with Indo-1/AM. After baseline pacing with a 400 ms interval, 1-25 ESC were interposed with a regular 160 ms interval followed by the postextrasystolic beat with a 400 ms interval. With an increase in the ESC number, left ventricular develop ed pressure and peak positive dP/dt increased in an exponential manner , reaching a plateau, that was the same for 3 extracellular Ca2+ ([Ca2 +](0); 0.55 (n = 9), 1.25 (n = 11) and 2.75 mM (n = 7). Increased [Ca2 +](0) shifted this relationship left and upward, and with 2.75 mM [Ca2 +](0) developed pressure and dP/dt decreased after the maximum potenti ation was obtained. The relationship between the ESC number and the am plitude of the Indo-1 fluorescence (F-400/F-510; an index of intracell ular Ca2+ ([Ca2+](i))) was also exponential and was shifted left and u pward by high [Ca2+](0); however, it lacked the declining phase. Thus, the relationship between the amplitude of F-400/F-510 and developed p ressure or dP/dt consisted of a positively linear part until the maxim um potentiation was obtained and a negatively linear with a further in crease in the amplitude of F-400/F-510. This observation suggests that although contractile potentiation is mediated by increased [Ca2+](i) transients, the maximum response might be determined by the responsive ness of the sarcomere.