Late Na(+) Current and Protracted Electrical Recovery Are Critical Determinants of the Aging Myopathy

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Nov 7

PMID 26541940

Citations 36

Authors

Sergio Signore

Andrea Sorrentino

Giulia Borghetti

Antonio Cannata

Marianna Meo

Yu Zhou

Ramaswamy Kannappan

Francesco Pasqualini

Heather OMalley

Mark Sundman

Nikolaos Tsigkas

Eric Zhang

Christian Arranto

Chiara Mangiaracina

Kazuya Isobe

Brena F Sena

JungHyun Kim

Polina Goichberg

Matthias Nahrendorf

Lori L Isom

Annarosa Leri

Piero Anversa

Marcello Rota

Affiliations

Soon will be listed here.

Abstract

The aging myopathy manifests itself with diastolic dysfunction and preserved ejection fraction. We raised the possibility that, in a mouse model of physiological aging, defects in electromechanical properties of cardiomyocytes are important determinants of the diastolic characteristics of the myocardium, independently from changes in structural composition of the muscle and collagen framework. Here we show that an increase in the late Na(+) current (INaL) in aging cardiomyocytes prolongs the action potential (AP) and influences temporal kinetics of Ca(2+) cycling and contractility. These alterations increase force development and passive tension. Inhibition of INaL shortens the AP and corrects dynamics of Ca(2+) transient, cell contraction and relaxation. Similarly, repolarization and diastolic tension of the senescent myocardium are partly restored. Thus, INaL offers inotropic support, but negatively interferes with cellular and ventricular compliance, providing a new perspective of the biology of myocardial aging and the aetiology of the defective cardiac performance in the elderly.

Citing Articles

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