Submitted on August 28, 2007
Accepted on March 24, 2008
Dopamine Increases L-type Calcium Current more in Newborn than Adult Rabbit Cardiomyocytes via D1 and 
2 Receptors
Guoliang Ding1, Rob F. Wiegerinck1, Ming Shen1, Anca Cojoc1, Carlo M. Zeidenweber1, and Mary B. Wagner1*
1 Department of Pediatrics, Emory University, Atlanta, Georgia, United States
* To whom correspondence should be addressed. E-mail: mary.wagner{at}emory.edu.
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 months) rabbit ventricular myocytes. Myocytes were enzymatically dissociated from NB and AD rabbit hearts. ICa was recorded using the whole cell patch-clamp technique. mRNA levels of cardiac dopamine receptor type 1 (D1), type 2 (D2) and 
-adrenergic receptors (-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 -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 -AR stimulation. Selective blockade of 1 or 2 receptors (with block of D1 receptors) showed that the -AR action of dopamine in the NB was largely mediated via 2-AR activation. Dopamine produces a larger increase in ICa in NB cardiomyocytes compared to ADs. The mechanism of action is not only through 2-adrenergic receptors but also due to higher expression of cardiac dopamine receptor type 1 in newborn.
