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

We investigated differences in L-type C[a.sup.2+] current (I[sub.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[sub.Ca] was smaller in INF myocytes (1.2 [+ or -] 0.1 pA/pF, n = 29, 6 [+ or -] 1 mo old, 11 patients) than in YAD (2.5 [+ or -] 0.2 pA/pF, n = 20, 16 [+ or -] 1 yr old, 5 patients) or AD (2.6 [+ or -] 0.3 pA/pF, n = 19, 66 [+ or -] 3 yr old, 9 patients) myocytes (P < 0.05). Maximal I[sub.Ca] produced by isoproterenol (Iso) was similar in INF, YAD, and AD ceils: 8.4 [+ or -] 1.1, 9.6 [+ or -] 1.0, and 9.2 [+ or -] 1.3 pA/pF, respectively. Efficacy ([E.sub.max]) was larger in INF (607 [+ or -] 50%) than for YAD (371 [+ or -] 29%) or AD (455 [+ or -] 12%) myocytes. Potency (E[C.sub.50]) was 8- to 10-fold higher in AD (0.82 [+ or -] 0.09 nM) or YAD (0.41 [+ or -] 0.14 nM) than in INF (7.6 [+ or -] 3.5 nM) myocytes. Protein levels were similar for [G.sub.i][[alpha].sub.2] but much greater for [G.sub.i][[alpha].sub.3] in INF than in AD or YAD atrial tissue. When [G.sub.i][[alpha].sub.3] activity was inhibited by inclusion of a [G.sub.i[alpha]3] COOH-terminal decapeptide in the pipette, basal [I.sub.Ca] and the response to 10 nM Iso were increased in INF, but not in YAD, cells. We propose that basal [I.sub.Ca] 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 [G.sub.i][[alpha].sub.3]. [beta]-adrenergic receptors; human atrium; atrial function; isoproterenol