Rosen M R, Danilo P, Robinson R B, Shah A, Steinberg S F
Department of Pharmacology, Columbia University, College of Physicians and Surgeons, New York, New York 10032.
Ann N Y Acad Sci. 1988;533:200-9. doi: 10.1111/j.1749-6632.1988.tb37249.x.
alpha 1-Adrenergic stimulation of the neonatal heart may induce either an increase or a decrease in ventricular automaticity, with the latter response predominating as age increases. We used isolated tissues from the hearts of neonatal and adult dogs and rats, as well as rat myocytes in tissue culture alone or in coculture with sympathetic nerves, to study the role of sympathetic innervation in modulating the alpha-adrenergic response. In the absence of sympathetic innervation, alpha-adrenergic stimulation uniformly increases automaticity. As the myocyte is innervated, an increased quantity of a GTP regulatory protein is detectable. That this protein is an essential transducer of alpha-adrenergic inhibition of automaticity is evidenced by the conversion of the alpha response from excitatory to inhibitory as the protein develops. ADP-ribosylation of the protein with pertussis toxin causes the alpha response to revert to excitation in both adult canine hearts and innervated myocytes in tissue culture. Hence, we have evidence for sympathetic modulation of cardiac rhythm via a regulatory protein whose function depends on normal neuronal development. Abnormal development of innervation may predispose to arrhythmogenesis via persistence of a primitive response to alpha stimulation.
α1肾上腺素能刺激新生心脏可能会导致心室自律性增加或降低，随着年龄增长，后一种反应占主导。我们使用新生和成年犬及大鼠心脏的离体组织，以及单独培养或与交感神经共培养的组织培养中的大鼠心肌细胞，来研究交感神经支配在调节α肾上腺素能反应中的作用。在没有交感神经支配的情况下，α肾上腺素能刺激会一致地增加自律性。随着心肌细胞被支配，可以检测到一种GTP调节蛋白的量增加。随着这种蛋白的发育，α反应从兴奋性转变为抑制性，这证明该蛋白是α肾上腺素能抑制自律性的重要转导因子。用百日咳毒素对该蛋白进行ADP核糖基化会使成年犬心脏和组织培养中的受支配心肌细胞的α反应恢复为兴奋。因此，我们有证据表明通过一种调节蛋白对心脏节律进行交感调节，该蛋白的功能取决于正常的神经元发育。神经支配的异常发育可能通过对α刺激的原始反应持续存在而导致心律失常的发生。
