ALPHA-ADRENERGIC MODIFICATION OF THE CA-2+ TRANSIENT AND CONTRACTION IN SINGLE-RAT CARDIOMYOCYTES

Intracellular Ca2+ transients and contraction were measured simultaneously in single rat cardiomyocytes loaded with the flurorescent 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 Hertz, α-adrenoceptor activation in the presence of β-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 contactility was proportional to the increase in peak cytosolic Ca2+, the effect of raising extracellular Ca2+ ([Ca2+]0) from 0.5 to 3 mm was examined in the absence and presence of α-adrenoceptor activation. At [Ca2+]0 concentrations up to 1 mm, α-adrenoceptor-mediated effects on contraction were directly correlated with changes in peak cytosolic Ca2+ and resembled the effect of raising [Ca2+]0 alone. In 2 and 3 mm [Ca2+]0, peak cytosolic Ca2+ approached a maximal level and α-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, β-adrenergic effects on shortening never exceeded those of α-adrenoceptor activation, although much higher peak cytosolic Ca2+ concentrations were achieved at high [Ca2+]0. The results suggest that the mechanism underlying the positive inotropic effect of α-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+. © 1992.