Mechanisms of Adenosine-Mediated Actions on Cellular and Clinical Cardiac Electrophysiology

To provide insights into the molecular mechanisms of adenosine-mediated cardiac cellular electrophysiology and how information about these mechanisms can be used to facilitate diagnostic and therapeutic approaches to various clinical arrhythmias. A review of (1) adenosine metabolism and receptors in the cardiac system, (2) adenosine-mediated signal transduction pathways in the regulation of cellular electrophysiology in various cardiac cell types, and (3) the clinical usefulness of adenosine in cardiac electrophysiology is presented. The effects of adenosine on cardiac electrophysiologic properties are consequences of complex interactions among the specific cardiac target structures, the density and type of adenosine receptors, and the effector systems. The easy application of adenosine and its short half-life, favorable sideeffects profile, and electrophysiologic properties make it an excellent diagnostic and therapeutic tool for the initial assessment of various tachyarrhythmias. The direct adenosine-activated K_ACh (potassium acetylcholine) channel signal transduction system explains the effects of adenosine on the sinus node, atrioventricular node, and atrial myocardium. The indirect adenosine-inhibited adenylate cyclase system accounts for its negative inotropic effects on the catecholamine-entrained contractility in atrial and ventricular myocardium. Because of the recent purification and cloning of adenosine receptors and subunits of G proteins, additional adenosine-mediated electrophysiologic mechanisms can be explored.