Cardiomyocyte ionic currents in intact young and aged murine Pgc-1β-/- atrial preparations.
Jiang, Anita Y
Mechanisms of ageing and development
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Valli, H., Ahmad, S., Jiang, A. Y., Smyth, R., Jeevaratnam, K., Matthews, H., & Huang, C. (2018). Cardiomyocyte ionic currents in intact young and aged murine Pgc-1β-/- atrial preparations.. Mechanisms of ageing and development, 169 1-9. https://doi.org/10.1016/j.mad.2017.11.016
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.
Heart Atria, Myocytes, Cardiac, Animals, Mice, Knockout, Mice, Potassium, Sodium, Ion Transport, Action Potentials, Aging, Arrhythmias, Cardiac, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Medical Research Council (MR/M001288/1)
British Heart Foundation (None)
Wellcome Trust (105727/Z/14/Z)
External DOI: https://doi.org/10.1016/j.mad.2017.11.016
This record's URL: https://www.repository.cam.ac.uk/handle/1810/273166
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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