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 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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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.
|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|
|Funders:||British Heart Foundation|
|Depositing User:||D Greensmith|
|Date Deposited:||21 Jan 2015 11:23|
|Last Modified:||23 Jan 2015 09:57|
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