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Cardiomyocyte ionic currents in intact young and aged murine Pgc-1β-/- atrial preparations.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Valli, Haseeb 
Ahmad, Shiraz 
Jiang, Anita Y 
Smyth, Robert 
Jeevaratnam, Kamalan 

Abstract

INTRODUCTION: Recent studies reported that energetically deficient murine Pgc-1β-/- hearts replicate age-dependent atrial arrhythmic phenotypes associated with their corresponding clinical conditions, implicating action potential (AP) conduction slowing consequent upon reduced AP upstroke rates. MATERIALS AND METHODS: We tested a hypothesis implicating Na+ current alterations as a mechanism underlying these electrophysiological phenotypes. We applied loose patch-clamp techniques to intact young and aged, WT and Pgc-1β-/-, atrial cardiomyocyte preparations preserving their in vivo extracellular and intracellular conditions. RESULTS AND DISCUSSION: Depolarising steps activated typical voltage-dependent activating and inactivating inward (Na+) currents whose amplitude increased or decreased with the amplitudes of the activating, or preceding inactivating, steps. Maximum values of peak Na+ current were independently influenced by genotype but not age or interacting effects of genotype and age on two-way ANOVA. Neither genotype, nor age, whether independently or interactively, influenced voltages at half-maximal current, or steepness factors, for current activation and inactivation, or time constants for recovery from inactivation following repolarisation. In contrast, delayed outward (K+) currents showed similar activation and rectification properties through all experimental groups. These findings directly demonstrate and implicate reduced Na+ in contrast to unchanged K+ current, as a mechanism for slowed conduction causing atrial arrhythmogenicity in Pgc-1β-/- hearts.

Description

Keywords

Age-dependent arrhythmia, Energetic deficiency, K(+) currents, Na(+) currents, Pgc-1β(−/−), Action Potentials, Aging, Animals, Arrhythmias, Cardiac, Heart Atria, Ion Transport, Mice, Mice, Knockout, Myocytes, Cardiac, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Potassium, Sodium

Journal Title

Mech Ageing Dev

Conference Name

Journal ISSN

0047-6374
1872-6216

Volume Title

169

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MR/M001288/1)
British Heart Foundation (None)
Wellcome Trust (105727/Z/14/Z)
British Heart Foundation (PG/15/12/31280)