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This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/H2327    most recent 00993.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ding, G. Articles by Wagner, M. B. Search for Related Content PubMed PubMed Citation Articles by Ding, G. Articles by Wagner, M. B.

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

Todd Franklin Cardiac Research Laboratory, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia

Submitted 28 August 2007 ; accepted in final form 24 March 2008

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 (I_Ca) 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. I_Ca 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 I_Ca more in NB (E_max 87 ± 10%) than in AD ventricular cells (E_max 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 I_Ca more in NB than AD cells. Additionally, SKF-38393 (selective D1 receptor agonist) significantly increased I_Ca 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 I_Ca 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 I_Ca 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.

development; β-adrenergic receptors; ventricle