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

Katsuko Egashira, Kiyomasa Nishii, Kei Ichiro Nakamura, Madoka Kumai, Sachio Morimoto, Yosaburo Shibata

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 Ca2+ 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.

Original languageEnglish
Pages (from-to)973-979
Number of pages7
JournalAnatomical Record - Part A Discoveries in Molecular, Cellular, and Evolutionary Biology
Volume280
Issue number2
DOIs
Publication statusPublished - Oct 2004

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Agricultural and Biological Sciences (miscellaneous)

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