Intracellular calcium transients in potentiated contractions induced by multiple extrasystolic beats in isolated perfused rat hearts.

Mechanisms underlying contractile potentiation induced by multiple extrasystolic 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 developed pressure and peak positive dP/dt increased in an exponential manner, reaching a plateau, that was the same for 3 extracellular Ca2+ ([Ca2+]o; 0.55 (n = 9), 1.25 (n = 11) and 2.75 mM (n = 7). Increased [Ca2+]o shifted this relationship left and upward, and with 2.75 mM [Ca2+]o developed pressure and dP/dt decreased after the maximum potentiation was obtained. The relationship between the ESC number and the amplitude of the Indo-1 fluorescence (F400/F510; an index of intracellular Ca2+ ([Ca2+]i)) was also exponential and was shifted left and upward by high [Ca2+]o; however, it lacked the declining phase. Thus, the relationship between the amplitude of F400/F510 and developed pressure or dP/dt consisted of a positively linear part until the maximum potentiation was obtained and a negatively linear part with a further increase in the amplitude of F400/F510. This observation suggests that although contractile potentiation is mediated by increased [Ca2+]i transients, the maximum response might be determined by the responsiveness of the sarcomere.