Effects of dopamine on L-type Ca2+ current in single atrial and ventricular myocytes of the rat

Abstract

1. The effects of dopamine on the L-type Ca2+ current (I(Ca,L) of both atrial and ventricular single myocytes and on the force of contraction of atrial trabeculae in rat heart were investigated. 2. Dopamine increased atrial I(Ca,L) at concentrations higher than 1 μM, but had little or no effect on I(Ca,L) at lower concentrations. The increase in I(Ca,L) at high concentrations was reversed by propranolol and acetylcholine, but not by phentolamine. Activation and inactivation kinetics of I(Ca,L) were not altered by dopamine. 3. In rat ventricular myocytes in which the D4 receptor mRNA does not express, dopamine (20-100 μM) also increased the I(Ca,L) amplitude and propranolol reversed this effect. 4. Clozapine, a potent D4 receptor antagonist, blocked the augmenting effect of dopamine on I(Ca,L) However, this effect could be explained by β-antagonism, since clozapine also inhibited the isoprenaline effect. 5. In the atrial trabeculae, the increase in contraction by dopamine (1 to 30 μM) was reversed by 1 μM propranolol, but not by 2 μM phentolamine. Low doses of dopamine (0.01 to 0.3 μM) did not affect the contraction in the controls or during a modest stimulation of the β-adrenoceptor with 0.01 μM isoprenaline. 6. These results indicate that the positive inotropic action of dopamine is mediated through direct stimulation of the β-adrenoceptor in both atrial and ventricular myocytes. Involvement of D4 receptor appears unlikely in the regulation of the atrial contraction.