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 Giα2 but much greater for Giα3 in INF than in AD or YAD atrial tissue. When Giα3 activity was inhibited by inclusion of a Giα3 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 β-adrenergic stimulation are inhibited in INF (but not YAD or AD) cells as a result of constitutive inhibitory effects of Giα3.
Calcium current depression in isolated human atrial myocytes after cessation of chronic treatment with calcium antagonists.