Developmental differences in L-type calcium current of human atrial myocytes

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 286; no. 5; pp. H1963 - H1969
• Main Authors: Tipparaju, Srinivas M, Kumar, Rajiv, Wang, Yanggan, Joyner, Ronald W, Wagner, Mary B
• Format: Journal Article
• Language: English
• Published: United States 01.05.2004
• Subjects: Adolescent; Adrenergic beta-Agonists - pharmacology; Aged; Aging - metabolism; Calcium Channels, L-Type - drug effects; Calcium Channels, L-Type - physiology; Cyclic AMP - pharmacology; Electrophysiology; Female; GTP-Binding Protein alpha Subunits, Gi-Go - chemistry; GTP-Binding Protein alpha Subunits, Gi-Go - metabolism; Heart Atria; Humans; Infant; Isoproterenol - pharmacology; Male; Middle Aged; Myocytes, Cardiac - metabolism; Peptide Fragments - pharmacology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01011.2003

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 Ca 2+ current ( I Ca ) 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 I Ca 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 I Ca 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 (E max ) was larger in INF (607 ± 50%) than for YAD (371 ± 29%) or AD (455 ± 12%) myocytes. Potency (EC 50 ) 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 G i 2 but much greater for G i 3 in INF than in AD or YAD atrial tissue. When G i 3 activity was inhibited by inclusion of a G i 3 COOH-terminal decapeptide in the pipette, basal I Ca and the response to 10 nM Iso were increased in INF, but not in YAD, cells. We propose that basal I Ca and the response to low-dose -adrenergic stimulation are inhibited in INF (but not YAD or AD) cells as a result of constitutive inhibitory effects of G i 3 . -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 ).