α-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 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⁺.