Conduction abnormality in gap junction protein connexin45-deficient embryonic stem cell-derived cardiac myocytes

The Anatomical Record. Part A, Discoveries in Molecular, Cellular, and Evolutionary Biology
Katsuko EgashiraYosaburo Shibata

Abstract

In early-stage heart, the cardiac impulse does not propagate through the specialized conduction system but spreads from myocyte to myocyte. We hypothesized that the gap junction protein connexin45 (Cx45) regulates early-stage contractions, because it is the only gap junction protein described in early hearts. Cx45-deficient (Cx45(-/-)) mice die of heart failure, concomitantly displaying other complex defects in the cardiovascular system. In order to determine the specific cardiac muscular function of Cx45, we created Cx45(-/-) embryonic stem (ES) cells to be differentiated into cardiac muscle in vitro. Unlike the coordinated contractions of wild-type cells, differentiated Cx45(-/-) cardiac myocytes showed high and irregular pulsation rates. Alterations of the electrophysiological properties of the Cx45(-/-) cardiac myocytes were indicated both by extracellular recording on planar multielectrode array probes and by intracellular Ca(2+) recording of the fluorescent Ca(2+) indicator fura-2. The in vitro system minimizes an influence of hemodynamic factors that complicate the phenotypes of Cx45(-/-) mice. Our results indicate that Cx45 is an essential connexin for coordinated conduction through early cardiac myocytes. The Supplemen...Continue Reading

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Citations

Feb 24, 2007·Analytical and Bioanalytical Chemistry·C K YeungS Ingebrandt
Dec 2, 2005·Anatomy and Embryology·Kiyomasa Nishii, Yosaburo Shibata
Aug 16, 2008·Stem Cell Reviews·Raymond C B WongAlice Pébay
Sep 27, 2008·Journal of Molecular and Cellular Cardiology·John P FahrenbachKathrin Banach
Nov 27, 2014·World Journal of Stem Cells·Kiyomasa NishiiYasushi Kobayashi
May 14, 2016·Zygote : the Biology of Gametes and Early Embryos·Kiyomasa NishiiYosaburo Shibata

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