Effects of dopamine on L‐type Ca 2+ current in single atrial and ventricular myocytes of the rat

The effects of dopamine on the L‐type Ca 2+ 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. Dopamine increased atrial I Ca,L at concentrations higher than 1 μ M , 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. In rat ventricular myocytes in which the D 4 receptor mRNA does not express, dopamine (20–100 μ M ) also increased the I Ca,L amplitude and propranolol reversed this effect. Clozapine, a potent D 4 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. In the atrial trabeculae, the increase in contraction by dopamine (1 to 30 μ M ) was reversed by 1 μ M propranolol, but not by 2 μ M phentolamine. Low doses of dopamine (0.01 to 0.3 μ M ) did not affect the contraction in the controls or during a modest stimulation of the β‐adrenoceptor with 0.01 μ M isoprenaline. 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 D 4 receptor appears unlikely in the regulation of the atrial contraction.