Reduced cardiomyocyte Na+ current in the age‐dependent murine Pgc‐1β −/− model of ventricular arrhythmia

Autor: Ahmad, Shiraz, Valli, Haseeb, Smyth, Robert, Jiang, Anita Y, Jeevaratnam, Kamalan, Matthews, Hugh R, Huang, Christopher L-H
Přispěvatelé: Smyth, Robert [0000-0001-9482-5123], Jeevaratnam, Kamalan [0000-0002-6232-388X], Huang, Christopher L-H [0000-0001-9553-6112], Apollo - University of Cambridge Repository
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Journal of Cellular Physiology
ISSN: 1097-4652
0021-9541
Popis: Peroxisome proliferator‐activated receptor‐γ coactivator‐1 deficient (Pgc‐1β −/−) murine hearts model the increased, age‐dependent, ventricular arrhythmic risks attributed to clinical conditions associated with mitochondrial energetic dysfunction. These were accompanied by compromised action potential (AP) upstroke rates and impaired conduction velocities potentially producing arrhythmic substrate. We tested a hypothesis implicating compromised Na+ current in these electrophysiological phenotypes by applying loose patch‐clamp techniques in intact young and aged, wild‐type (WT) and Pgc‐1β −/−, ventricular cardiomyocyte preparations for the first time. This allowed conservation of their in vivo extracellular and intracellular conditions. Depolarising steps elicited typical voltage‐dependent activating and inactivating inward Na+ currents with peak amplitudes increasing or decreasing with their respective activating or preceding inactivating voltage steps. Two‐way analysis of variance associated Pgc‐1β −/− genotype with independent reductions in maximum peak ventricular Na+ currents from −36.63 ± 2.14 (n = 20) and −35.43 ± 1.96 (n = 18; young and aged WT, respectively), to −29.06 ± 1.65 (n = 23) and −27.93 ± 1.63 (n = 20; young and aged Pgc‐1β −/−, respectively) pA/μm2 (p
Databáze: OpenAIRE
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