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

Clarke, JD; Caldwell, JL; Horn, MA; Bode, EF; Richards, MA; Hall, MCS; Graham, HK; Briston, SJ; Greensmith, DJ; Eisner, DA; Dibb, KM; Trafford, AW

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 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 (kSR, by 32%), L-type Ca(2+) current density (by 36%) and action potential duration (APD90 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 (ICa-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, ICa-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 ICa-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.

Citation

Clarke, J., Caldwell, J., Horn, M., Bode, E., Richards, M., Hall, M., …Trafford, A. (2015). Perturbed atrial calcium handling in an ovine model of heart failure : potential roles for reductions in the L-type calcium current. Journal of Molecular and Cellular Cardiology, 79, 169-179. https://doi.org/10.1016/j.yjmcc.2014.11.017

• Journal Article Type: Article
• Acceptance Date: Nov 11, 2014
• Online Publication Date: Nov 22, 2014
• Publication Date: Feb 1, 2015
• Deposit Date: Jan 21, 2015
• Journal: Journal of Molecular and Cellular Cardiology
• Print ISSN: 0022-2828
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 79
• Pages: 169-179
• DOI: https://doi.org/10.1016/j.yjmcc.2014.11.017
• Publisher URL: http://dx.doi.org/10.1016/j.yjmcc.2014.11.017