Cardiomyocyte ionic currents in intact young and aged murine Pgc-1β−/− atrial preparations. (January 2018)

• Record Type: Journal Article
• Authors: Valli, Haseeb; Ahmad, Shiraz; Jiang, Anita Y.; Smyth, Robert; Jeevaratnam, Kamalan; Matthews, Hugh R.; Huang, Christopher L.-H.
• Is Part Of: Mechanisms of ageing and development. Volume 169(2018)
• Page Start: 1
• Page End: 9
• Publication Date: 2018-01
• Subjects: Na+ currents -- K+ currents -- Age-dependent arrhythmia -- Pgc-1β−/− -- Energetic deficiency; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2017.11.016
• Languages: English
• ISSNs: 0047-6374

Abstract

Graphical abstract: Highlights: Energetically-deficient Pgc-1β−/− murine atria show age-dependent arrhythmia. Voltage clamp studies investigated their underlying membrane current changes. Pgc-1β−/− atria showed reduced inward Na + currents with normal voltage-dependences. Outward repolarising K+ currents retained normal activation and rectification. A resulting slowed action potential conduction explains the arrhythmic phenotype. 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.