β2-adrenoceptors and ventricular fibrillation

beta -Adrenoceptor antagonists significantly reduce the incidence of sudden cardiac death in patients with contractile dysfunction. Contractile dysfunction is associated with a decline in beta (1)-adrenoceptors, no change in the number of beta (2)-adrenoceptors, and an increased responsiveness to beta (2)-adrenoceptor stimulation. Selective beta (2)-adrenoceptor blockade prevents ventricular fibrillation in a canine model of sudden cardiac death. Cardiac beta (2)-adrenoceptor stimulation increases L-type Ca2+ currents, but unlike beta (1)-adrenoceptor stimulation, it fails to elicit phospholamban phosphorylation, Restoration of resting diastolic [Ca2+] following beta (2)-adrenoceptor-mediated increases in Ca2+ influx is more dependent on Na+/Ca2+ exchange, which generates an arrhythmogenic transient inward current that can trigger ventricular fibrillation. (C) 2000 Elsevier Science Inc. All rights reserved.