Tipparaju Srinivas M, Kumar Rajiv, Wang Yanggan, Joyner Ronald W, Wagner Mary B
Todd Franklin Cardiac Research Laboratory, The Sibley Children's Heart Center, Depertment of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1963-9. doi: 10.1152/ajpheart.01011.2003. Epub 2004 Jan 8.
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.
我们研究了取自右心耳活检的婴儿（INF，1至12个月大）、青年（YAD，14至18岁）和老年（AD）心肌细胞之间L型钙电流（ICa）的差异。INF心肌细胞的基础ICa（1.2±0.1 pA/pF，n = 29，6±1个月大，11例患者）小于YAD（2.5±0.2 pA/pF，n = 20，16±1岁，5例患者）或AD（2.6±0.3 pA/pF，n = 19，66±3岁，9例患者）心肌细胞（P<0.05）。异丙肾上腺素（Iso）产生的最大ICa在INF、YAD和AD细胞中相似：分别为8.4±1.1、9.6±1.0和9.2±1.3 pA/pF。效能（Emax）在INF（607±50%）中大于YAD（371±29%）或AD（455±12%）心肌细胞。效力（EC50）在AD（0.82±0.09 nM）或YAD（0.41±0.14 nM）中比INF（7.6±3.5 nM）心肌细胞高8至10倍。INF心房组织中Gialpha2的蛋白水平相似，但Gialpha3的蛋白水平比AD或YAD高得多。当通过在移液管中加入Gialpha3羧基末端十肽抑制Gialpha3活性时，INF细胞中的基础ICa和对10 nM Iso的反应增加，但YAD细胞中没有增加。我们提出，由于Gialpha3的组成性抑制作用，INF（但不是YAD或AD）细胞中的基础ICa和对低剂量β-肾上腺素能刺激的反应受到抑制。
