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Advisor(s)
Abstract(s)
The cardiac L-type Ca2+ channel current (ICa) is an important determinant of myocardial contractility. Its regulation by neurotransmitters, hormones, and paracrine factors contributes to the control of cardiac output to meet the demands of the body. A large number of these extracellular first messengers, acting on specific membrane receptors in cardiac myocytes, regulate the activity of adenylyl cyclase which in turn controls the intracellular concentration of cAMP, the activity of the cAMPdependent protein kinase (PKA), and the degree of phosphorylation and stimulation of L-type Ca2+ channels (Hartzell, 1988; McDonald et al. 1994; Hove-Madsen et al. 1996; Striessnig, 1999). A typical example of such regulation is the control of heart function by the sympathetic and parasympathetic nervous systems, which act via adrenoceptors and muscarinic receptors (Brodde & Michel, 1999). In addition to the cAMP cascade, other factors regulate heart function by acting primarily on the cGMP cascade; these include atrial and brain natriuretic peptides (de Bold et al.1996) and nitric oxide (NO) (Paulus & Shah, 1999; Shah & MacCarthy, 2000).