Regulation of the Gs Protein in the Heart

Abstract

The role of GTP-binding proteins (G proteins) as transducers of information across the plasma membrane is now well-established. A wide variety of hormones and neurotransmitters that regulate the heart and vascular system have been shown to produce their effects by the activation of such proteins (1). Acetylcholine released by post¬ganglionic parasympathetic (vagal) neurons and norepinephrine released at postganglionic sympathetic neurons are the most physiologically important of these agonists. Norepinephrine and epinephrine, a circulating hormone principally derived from the adrenal medulla, activate cardiac β1and β2-adrenergic receptors to produce chrono¬tropic, dromotropic, lusitropic and inotropic actions, β-adrenergic receptors exert these actions via their ability to activate the stimulatory GTP binding protein, Gs. Gs, in turn, promotes the physiological responses via the regulation of effector molecules. In this article, we will address 4 questions regarding cardiac Gs: 1) What are the effector molecules regulated by Gs? 2) How much Gs is present in cardiac membrane preparations? 3) Is Gs exclusively localized to the cardiac sarcolemma? 4) Is Gs altered physiologically or during cardiac disease?