Hormonal and Non-Hormonal Regulation of Ca2+ Current and Adenylate Cyclase in Cardiac Cells
The influx of Ca2+ ions through transmembrane Ca2+ channels is fundamental in many aspects of cardiac function. Regulation of the heart beat by noradrenaline and acetylcholine (ACh) is in part mediated by the effects of these neurotransmitters on calcium current, ICa (1). β-adrenergic stimulation of ICa is mediated by a guanine-nucleotide binding protein, Gs (2), which triggers the activation of adenylate cyclase (AC) and in turn stimulates cAMP-dependent phosphorylation of Ca2+ channels (1,3). Gs has also been shown to directly activate Ca2+ channels (4). This latter mechanism, however, may play only a minor role in the physiological response to noradrenaline since the effects of β-adrenergic agonists on ICa were mimicked by external application of cAMP, its analogues or phosphodiesterase inhibitors (5), forskolin (6) [a direct activator of AC (7)], and by intracellular application of cAMP (8,9) or the catalytic subunit of cAMP-dependent protein kinase (PKA; ref. 8).
KeywordsNoradrenaline Catecholamine Cardiol Acetylcholine Creatine
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