Calcium and Cardiac Arrhythmias: DADs, EADs, and Alternans

Rapid progress has been made in understanding the molecular mechanisms by which calcium ions mediate certain cardiac arrhythmias. Principal advances include imaging of cytosolic calcium in isolated cells and in intact tissues, use of fluorescent indicators and monophasic action potentials to record membrane potentials in isolated tissue, and sequencing of the genes that encode critical ion channel proteins. In this review, five types of arrhythmias are discussed where calcium ion currents, or currents controlled by calcium, appear to be responsible for arrythmogenesis. These include: (1) the delayed afterpotential that occurs in conditions of intracellular calcium overload such as digitalis toxicity; (2) the early afterdepolarization that occurs when action potential duration is prolonged; (3) the slowly conducted calcium-dependent action potential (the slow response) in the SA and AV nodes; (4) the phenomenon of calcium transient alternans during ischemia, which is related to action potential duration alternans and t-wave alternans; (5) catecholamine-induced cardiac arrhythmias in families with mutations of the sarcoplasmic reticulum calcium-release channel. For each type of arrhythmia, the clinical implications of emerging knowledge are discussed. An especially important issue is whether ventricular fibrillation during acute coronary artery occlusion is due to calcium transient alternans. Ventricular fibrillation due to acute ischemia is an important subset of the 400,000 sudden cardiac deaths that occur annually in the U.S. Certain drugs, including beta blockers, fish oils, verapamil, and diltiazem, seem to specifically prevent ventricular fibrillation in this setting, and in most cases an effect of the drug on cytosolic calcium appears to be involved. Referee: David S. Rosenbaum, Heart and Vascular Center, Metro Health Campus, Case Western Reserve University, 2500 Metro Health Drive, Hamann 3, Cleveland, OH 44109-1998. Tel: 216-778-2005. Fax: 216-778-4294