Alpha-adrenergic modification of the Ca2+ transient and contraction in single rat cardiomyocytes.

Intracellular Ca2+ transients and contraction were measured simultaneously in single rat cardiomyocytes loaded with the fluorescent Ca2+ indicator fura-2, using a recently described high-speed digital imaging method (O'Rourke et al., 1990, Am J Physiol 259: H230-H242). In cardiomyocytes electrically-stimulated at 1 Hertz, alpha-adrenoceptor activation in the presence of beta-adrenoceptor blockade resulted in enhanced cell shortening associated with an increase in the amplitude of the cytosolic Ca2+ transient. Both effects developed in parallel over a 10-min time period and occurred without a change in the half-times for decay of Ca2+ or relaxation of the cell. To determine if the increase in contractility was proportional to the increase in peak cytosolic Ca2+, the effect of raising extracellular Ca2+ ([Ca2+]o) from 0.5 to 3 mM was examined in the absence and presence of alpha-adrenoceptor activation. At [Ca2+]o concentrations up to 1 mM, alpha-adrenoceptor-mediated effects on contraction were directly correlated with changes in peak cytosolic Ca2+ and resembled the effect of raising [Ca2+]o alone. In 2 and 3 mM [Ca2+]o, peak cytosolic Ca2+ approached a maximal level and alpha-adrenoceptor activation induced a slight enhancement in the extent of shortening in the absence of a detectable alteration of the Ca2+ transient. In contrast, under similar conditions, beta-adrenergic effects on shortening never exceeded those of alpha-adrenoceptor activation, although much higher peak cytosolic Ca2+ concentrations were achieved at high [Ca2+]o. The results suggest that the mechanism underlying the positive inotropic effect of alpha-adrenergic stimulation in rat ventricular cells is primarily dependent on an enhancement of the cytosolic Ca2+ transient, although there is also an increase in the myofibrillar response to intracellular Ca2+ under the condition of high extracellular Ca2+.