Perturbed atrial calcium handling in an ovine model of heart failure: Potential roles for reductions in the L-type calcium current

Abstract

Heart failure (HF) is commonly associated with reduced cardiac output and an increased risk of atrial arrhythmias particularly during β-adrenergic stimulation. The aim of the present study was to determine how HF alters systolic Ca2+ and the response to β-adrenergic (β-AR) stimulation in atrial myocytes. HF was induced in sheep by ventricular tachypacing and changes in intracellular Ca2+ concentration studied in single left atrial myocytes under voltage and current clamp conditions. The following were all reduced in HF atrial myocytes; Ca2+ transient amplitude (by 46% in current clamped and 28% in voltage clamped cells), SR dependent rate of Ca2+ removal (kSR, by 32%), L-type Ca2+ current density (by 36%) and action potential duration (APD90 by 22%). However, in HF SR Ca2+ content was increased (by 19%) when measured under voltage-clamp stimulation. Inhibiting the L-type Ca2+ current (ICa-L) in control cells reproduced both the decrease in Ca2+ transient amplitude and increase of SR Ca2+ content observed in voltage-clamped HF cells. During β-AR stimulation Ca2+ transient amplitude was the same in control and HF cells. However, ICa-L remained less in HF than control cells whilst SR Ca2+ content was highest in HF cells during β-AR stimulation. The decrease in ICa-L that occurs in HF atrial myocytes appears to underpin the decreased Ca2+ transient amplitude and increased SR Ca2+ content observed in voltage-clamped cells.