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 ORCID: https://orcid.org/0000-0002-6459-523X, Eisner, DA, Dibb, KM and Trafford, AW 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 , pp. 169-179.

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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.

Item Type:	Article
Themes:	Health and Wellbeing Subjects outside of the University Themes
Schools:	Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title:	Journal of Molecular and Cellular Cardiology
Publisher:	Elsevier
Refereed:	Yes
Funders:	British Heart Foundation
Depositing User:	D Greensmith
Date Deposited:	21 Jan 2015 11:23
Last Modified:	21 Nov 2018 20:18
URI:	http://usir.salford.ac.uk/id/eprint/33355

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