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.

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