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Am J Physiol Heart Circ Physiol (January 8, 2004). doi:10.1152/ajpheart.01011.2003
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Submitted on October 24, 2003
Accepted on January 2, 2004

Developmental Differences in L-type Calcium Current of Human Atrial Myocytes

Srinivas M. Tipparaju1, Rajiv Kumar1, Yanggan Wang1, Ronald W. Joyner1, and Mary B. Wagner1*

1 The Sibley Children's Heart Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA

* To whom correspondence should be addressed. E-mail: mwagner{at}cellbio.emory.edu.

We investigated differences in L-type Calcium current (ICa) between infant (INF, 1-12 month), young adult (YAD, 14-18 years), and older adult (AD) myocytes from biopsies of right atrial appendages. Basal ICa in INF myocytes (1.2 ± 0.1 pA/pF, n=29, age 6 ± 1 months, 11 patients) was smaller (p<0.05) than either YAD (2.5 ± 0.2 pA/pF, n=20, age 16 ± 1 years, 5 patients) or AD (2.6 ± 0.3 pA/pF, n=19, age 66 ± 3 years, 9 patients) myocytes. Maximal ICa produced by isoproterenol (ISO) was similar for INF (8.4 ± 1.1 pA/pF), YAD (9.6 ± 1.0 pA/pF), and AD (9.2 ± 1.3 pA/pF) cells. Efficacy was larger for INF (Emax 607 ± 50 %), than for YAD (Emax 371 ± 29%) or AD (Emax 455 ± 12 %) myocytes. Potency was 8-10 fold higher for AD (EC50 = 0.82 ± 0.09 nM) or YAD (EC50 = 0.41 ± 0.14 nM ) than for INF myocytes (EC50 = 7.6 ± 3.5 nM). Protein levels were similar for Gi{alpha}2 but much greater for Gi{alpha}3 in INF vs. AD or YAD atrial tissue. When Gi{alpha}3 activity was inhibited by including a Gi{alpha}3 C-terminal decapeptide in the pipette, basal ICa and the response to 10 nM ISO were increased for INF cells but not for 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 by constitutive inhibitory effects of Gi{alpha}3 in INF cells.




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[Abstract] [Full Text] [PDF]


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