title: Dopamine increases L-type calcium current more in newborn than adult rabbit cardiomyocytes via D1 and beta2 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 (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 beta-adrenergic receptors (beta-ARs) were measured by real-time RT-PCR. Dopamine (100 microM) 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 beta-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 beta-AR stimulation. Selective blockade of beta(1)- or beta(2)-receptors (with block of D1 receptors) showed that the beta-AR action of dopamine in the NB was largely mediated via beta(2)-AR activation. Dopamine produces a larger increase in I(Ca) in NB cardiomyocytes compared with ADs. The mechanism of action is not only through beta(2)-ARs but also due to higher expression of cardiac D1 receptor in NB.
authors: Department of Pediatrics, Emory University School of Medicine, 2015 Uppergate Drive 336, Atlanta, GA 30322, USA.
authors: Guoliang
authors: G
authors: Ding
authors: Rob F
authors: RF
authors: Wiegerinck
authors: Ming
authors: M
authors: Shen
authors: Anca
authors: A
authors: Cojoc
authors: Carlo M
authors: CM
authors: Zeidenweber
authors: Mary B
authors: MB
authors: Wagner
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D000319:Adrenergic beta-Antagonists; D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D002118:Calcium; D004298:Dopamine