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

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 Ca(2 +) and the response to β-adrenergic (β-AR) stimulation in atrial myocytes. HF was induced in sheep by ventricular tachypacing and changes in intracellular Ca(2 +) concentration studied in single left atrial myocytes under voltage and current clamp conditions. The following were all reduced in HF atrial myocytes; Ca(2 +) transient amplitude (by 46% in current clamped and 28% in voltage clamped cells), SR dependent rate of Ca(2 +) removal (k(SR), by 32%), L-type Ca(2 +) current density (by 36%) and action potential duration (APD(90) by 22%). However, in HF SR Ca(2 +) content was increased (by 19%) when measured under voltage-clamp stimulation. Inhibiting the L-type Ca(2 +) current (I(Ca-L)) in control cells reproduced both the decrease in Ca(2 +) transient amplitude and increase of SR Ca(2 +) content observed in voltage-clamped HF cells. During β-AR stimulation Ca(2 +) transient amplitude was the same in control and HF cells. However, I(Ca-L) remained less in HF than control cells whilst SR Ca(2 +) content was highest in HF cells during β-AR stimulation. The decrease in I(Ca-L) that occurs in HF atrial myocytes appears to underpin the decreased Ca(2 +) transient amplitude and increased SR Ca(2 +) content observed in voltage-clamped cells.