Developmental differences in L-type calcium current of human atrial myocytes.
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 Gialpha2 but much greater for Gialpha3 in INF than in AD or YAD atrial tissue. When Gialpha3 activity was inhibited by inclusion of a Gialpha3 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 Gialpha3.
Tipparaju
Srinivas M
SM
Todd Franklin Cardiac Research Laboratory, The Sibley Children's Heart Center, Depertment of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Kumar
Rajiv
R
Wang
Yanggan
Y
Joyner
Ronald W
RW
Wagner
Mary B
MB
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000368:Aged; D000375:Aging / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000737:chemistry / Q000378:metabolism; D006325:Heart Atria; D006801:Humans; D007223:Infant; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D020746:Calcium Channels, L-Type; D010446:Peptide Fragments; D000242:Cyclic AMP; C498819:GNAI3 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D007545:Isoproterenol