Dopamine increases L-type calcium current more in newborn than adult rabbit cardiomyocytes via D1 and β2 receptors

Abstract

Dopamine is used to treat heart failure, particularly after cardiac surgery in infants, but the mechanisms of action are unclear. We investigated differences in the effect of dopamine on L-type calcium current ( ICa) between newborn (NB, 1–4 days) and adult (AD, 3–4 mo) rabbit ventricular myocytes. Myocytes were enzymatically dissociated from NB and AD rabbit hearts. ICa was recorded by using the whole cell patch-clamp technique. mRNA levels of cardiac dopamine receptor type 1 (D1), type 2 (D2), and β-adrenergic receptors (β-ARs) were measured by real-time RT-PCR. Dopamine (100 μM) increased ICa more in NB (Emax 87 ± 10%) than in AD ventricular cells (Emax 21 ± 3%). Further investigation of this difference showed that mRNA levels of the D1 receptor were significantly higher in NB, and, with β-AR blockade, dopamine increased ICa more in NB than AD cells. Additionally, SKF-38393 (selective D1 receptor agonist) significantly increased ICa by 55 ± 4% in NB ( P < 0.05, n = 4) and by 11 ± 1% in AD ( P < 0.05, n = 6). Dopamine in the presence of SCH-23390 (D1 receptor antagonist) increased ICa in NB cells by 67 ± 5% and by 22 ± 2% in AD cells, suggesting a role for β-AR stimulation. Selective blockade of β1- or β2-receptors (with block of D1 receptors) showed that the β-AR action of dopamine in the NB was largely mediated via β2-AR activation. Dopamine produces a larger increase in ICa in NB cardiomyocytes compared with ADs. The mechanism of action is not only through β2-ARs but also due to higher expression of cardiac D1 receptor in NB.