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Am J Physiol Heart Circ Physiol 286: H1963-H1969, 2004. First published January 8, 2004; doi:10.1152/ajpheart.01011.2003
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Developmental differences in L-type calcium current of human atrial myocytes

Srinivas M. Tipparaju, Rajiv Kumar, Yanggan Wang, Ronald W. Joyner, and Mary B. Wagner

Todd Franklin Cardiac Research Laboratory, Sibley Children's Heart Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322

Submitted 24 October 2003 ; accepted in final form 2 January 2004

We investigated differences in L-type Ca2+ current (ICa) between infant (INF, 1–12 mo old), young adult (YAD, 14–18 yr old), and older adult (AD) myocytes from biopsies of right atrial appendages. Basal ICa was smaller in INF myocytes (1.2 ± 0.1 pA/pF, n = 29, 6 ± 1 mo old, 11 patients) than in YAD (2.5 ± 0.2 pA/pF, n = 20, 16 ± 1 yr old, 5 patients) or AD (2.6 ± 0.3 pA/pF, n = 19, 66 ± 3 yr old, 9 patients) myocytes (P < 0.05). Maximal ICa produced by isoproterenol (Iso) was similar in INF, YAD, and AD cells: 8.4 ± 1.1, 9.6 ± 1.0, and 9.2 ± 1.3 pA/pF, respectively. Efficacy (Emax) was larger in INF (607 ± 50%) than for YAD (371 ± 29%) or AD (455 ± 12%) myocytes. Potency (EC50) was 8- to 10-fold higher in AD (0.82 ± 0.09 nM) or YAD (0.41 ± 0.14 nM) than in INF (7.6 ± 3.5 nM) myocytes. Protein levels were similar for Gi{alpha}2 but much greater for Gi{alpha}3 in INF than in AD or YAD atrial tissue. When Gi{alpha}3 activity was inhibited by inclusion of a Gi{alpha}3 COOH-terminal decapeptide in the pipette, basal ICa and the response to 10 nM Iso were increased in INF, but not in YAD, cells. We propose that basal ICa and the response to low-dose {beta}-adrenergic stimulation are inhibited in INF (but not YAD or AD) cells as a result of constitutive inhibitory effects of Gi{alpha}3.

{beta}-adrenergic receptors; human atrium; atrial function; isoproterenol


Address for reprint requests and other correspondence: M. B. Wagner, Todd Franklin Cardiac Research Laboratory, The Sibley Children's Heart Center, Dept. of Pediatrics, Emory Univ. School of Medicine, 2040 Ridgewood Dr. NE, Atlanta, GA 30322 (E-mail: mwagner{at}cellbio.emory.edu).




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G. Ding, R. F. Wiegerinck, M. Shen, A. Cojoc, C. M. Zeidenweber, and M. B. Wagner
Dopamine increases L-type calcium current more in newborn than adult rabbit cardiomyocytes via D1 and {beta}2 receptors
Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2327 - H2335.
[Abstract] [Full Text] [PDF]


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