title: beta(2)-Adrenoceptors and ventricular fibrillation.
abstract: 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 Ca(2+) currents, but unlike beta(1)-adrenoceptor stimulation, it fails to elicit phospholamban phosphorylation. Restoration of resting diastolic [Ca(2+)] following beta(2)-adrenoceptor-mediated increases in Ca(2+) influx is more dependent on Na(+)/Ca(2+) exchange, which generates an arrhythmogenic transient inward current that can trigger ventricular fibrillation.
authors.affiliation: Department of Medical Biochemistry, The Ohio State University College of Medicine and Public Health, 333 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210-1218, USA.Altschund.2@osu.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Altschuld
authors.forename: G E
authors.initials: GE
authors.lastname: Billman
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D004285:Dogs; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D018343:Receptors, Adrenergic, beta-2 / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D014693:Ventricular Fibrillation / Q000188:drug therapy*
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018343:Receptors, Adrenergic, beta-2