α-Adrenergic modification of the Ca 2+ transient and contraction in single rat cardiomyocytes

Abstract

Intracellular Ca 2+ transients and contraction were measured simultaneously in single rat cardiomyocytes loaded with the flurorescent Ca 2+ 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 Ca 2+ transient. Both effects developed in parallel over a 10-min time period and occurred without a change in the half-times for decay of Ca 2+ or relaxation of the cell. To determine if the increase in contactility was proportional to the increase in peak cytosolic Ca 2+, the effect of raising extracellular Ca 2+ ([Ca 2+] 0) from 0.5 to 3 m m was examined in the absence and presence of α-adrenoceptor activation. At [Ca 2+] 0 concentrations up to 1 m m, α-adrenoceptor-mediated effects on contraction were directly correlated with changes in peak cytosolic Ca 2+ and resembled the effect of raising [Ca 2+] 0 alone. In 2 and 3 m m [Ca 2+] 0, peak cytosolic Ca 2+ 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 Ca 2+ transient. In contrast, under similar conditions, β-adrenergic effects on shortening never exceeded those of α-adrenoceptor activation, although much higher peak cytosolic Ca 2+ concentrations were achieved at high [Ca 2+] 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 Ca 2+ transient, although there is also an increase in the myofibrillar response to intracellular Ca 2+ under the condition of high extracellular Ca 2+.