title: Atrial L-type Ca2+ currents and human atrial fibrillation.
abstract: Chronic atrial fibrillation (AF) is characterized by decreased atrial contractility, shortened action potential duration, and decreased accommodation of action potential duration to changes in activation rate. Studies on experimental animal models of AF implicate a reduction in L-type Ca2+ current (I(Ca)) density in these changes. To evaluate the effect of AF on human I(Ca), we compared I(Ca) in atrial myocytes isolated from 42 patients in normal sinus rhythm at the time of cardiac surgery with that of 11 chronic AF patients. I(Ca) was significantly reduced in the myocytes of patients with chronic AF (mean -3.35+/-0.5 pA/pF versus -9.13+/-1. 0 pA/pF in the controls), with no difference between groups in the voltage dependence of activation or steady-state inactivation. Although I(Ca) was lower in myocytes from the chronic AF patients, their response to maximal beta-adrenergic stimulation was not impaired. Postoperative AF frequently follows cardiac surgery. Half of the patients in the control group (19/38) of this study experienced postoperative AF. Whereas chronic AF is characterized by reduced atrial I(Ca), the patients with the greatest I(Ca) had an increased incidence of postoperative AF, independent of patient age or diagnosis. This observation is consistent with the concept that calcium overload may be an important factor in the initiation of AF. The reduction in functional I(Ca) density in myocytes from the atria of chronic AF patients may thus be an adaptive response to the arrhythmia-induced calcium overload.
authors.affiliation: Department of Cardiology and Kaufman Center for Heart Failure, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. vanwagd@ccf.org
authors.forename: D R
authors.initials: DR
authors.lastname: Van Wagoner
authors.forename: A L
authors.initials: AL
authors.lastname: Pond
authors.forename: M
authors.initials: M
authors.lastname: Lamorgese
authors.forename: S S
authors.initials: SS
authors.lastname: Rossie
authors.forename: P M
authors.initials: PM
authors.lastname: McCarthy
authors.forename: J M
authors.initials: JM
authors.lastname: Nerbonne
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology* / Q000601:surgery; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020746:Calcium Channels, L-Type; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D001026:Coronary Artery Bypass; D004198:Disease Susceptibility; D005260:Female; D005786:Gene Expression Regulation; D006325:Heart Atria / Q000473:pathology / Q000503:physiopathology; D006329:Heart Conduction System / Q000503:physiopathology; D016027:Heart Transplantation; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011183:Postoperative Complications / Q000503:physiopathology
chemical_list: D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D009543:Nifedipine; D007545:Isoproterenol; D002118:Calcium