Sympathetic neural and alpha-adrenergic modulation of arrhythmias.
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.
Rosen
M R
MR
Department of Pharmacology, Columbia University, College of Physicians and Surgeons, New York, New York 10032.
Danilo
P
P
Robinson
R B
RB
Shah
A
A
Steinberg
S F
SF
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D004285:Dogs; D006321:Heart / Q000294:innervation*; D006801:Humans; D011690:Purkinje Fibers / Q000502:physiology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013398:Sudden Infant Death / Q000209:etiology*; D013564:Sympathetic Nervous System / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha