T-tubule Remodeling and Increased Heterogeneity of Calcium Release During the Progression to Heart Failure in Intact Rat Ventricle

Overview

Journal Physiol Rep

Specialty Physiology

Date 2017 Dec 28

PMID 29279414

Citations 12

Authors

Jasleen K Singh

Varderes Barsegyan

Nikhil Bassi

William Marszalec

Shannon Tai

Shruthi Mothkur

Maaz Mulla

Elsa Nico

Yohannes Shiferaw

Gary L Aistrup

John Andrew Wasserstrom

Affiliations

Soon will be listed here.

Abstract

A highly organized transverse-tubule (TT) system is essential to normal Ca cycling and cardiac function. We explored the relationship between the progressive disruption of TTs and resulting Ca cycling during the development of heart failure (HF). Confocal imaging was used to measure Ca transients and 2-D z-stack images in left ventricular epicardial myocytes of intact hearts from spontaneously hypertensive rats (SHR) and Wistar-Kyoto control rats. TT organization was measured as the organizational index (OI) derived from a fast Fourier transform of TT organization. We found little decrease in the synchrony of Ca release with TT loss until TT remodeling was severe, suggesting a TT "reserve" characterized by a wide range of TT remodeling with little effect on synchrony of release but beyond which variability in release shows an accelerating sensitivity to TT loss. To explain this observation, we applied a computational model of spatially distributed Ca signaling units to investigate the relationship between OI and excitation-contraction coupling. Our model showed that release heterogeneity exhibits a nonlinear relationship on both the spatial distribution of release units and the separation between L-type Ca channels and ryanodine receptors. Our results demonstrate a unique relationship between the synchrony of Ca release and TT organization in myocytes of intact rat ventricle that may contribute to both the compensated and decompensated phases of heart failure.

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