The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

179 Scopus Citations
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Author(s)

  • Danny L. Costantini
  • Eric P. Arruda
  • Pooja Agarwal
  • Kyoung-Han Kim
  • Yonghong Zhu
  • Wei Zhu
  • Melanie Lebel
  • Chi Wa Cheng
  • Chong Y. Park
  • Stephanie A. Pierce
  • Alejandra Guerchicoff
  • Guido D. Pollevick
  • Toby Y. Chan
  • M. Golam Kabir
  • Mansoor Husain
  • Charles Antzelevitch
  • Deepak Srivastava
  • Gil J. Gross
  • Chi-Chung Hui
  • Peter H. Backx
  • Benoit G. Bruneau

Detail(s)

Original languageEnglish
Pages (from-to)347-358
Journal / PublicationCell
Volume123
Issue number2
Publication statusPublished - 21 Oct 2005

Abstract

Rhythmic cardiac contractions depend on the organized propagation of depolarizing and repolarizing wavefronts. Repolarization is spatially heterogeneous and depends largely on gradients of potassium currents. Gradient disruption in heart disease may underlie susceptibility to fatal arrhythmias, but it is not known how this gradient is established. We show that, in mice lacking the homeodomain transcription factor Irx5, the cardiac repolarization gradient is abolished due to increased Kv4.2 potassium-channel expression in endocardial myocardium, resulting in a selective increase of the major cardiac repolarization current, Ito,f, and increased susceptibility to arrhythmias. Myocardial Irx5 is expressed in a gradient opposite that of Kv4.2, and Irx5 represses Kv4.2 expression by recruiting mBop, a cardiac transcriptional repressor. Thus, an Irx5 repressor gradient negatively regulates potassium-channel-gene expression in the heart, forming an inverse Ito,f gradient that ensures coordinated cardiac repolarization while also preventing arrhythmias. Copyright ©2005 by Elsevier Inc.

Citation Format(s)

The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient. / Costantini, Danny L.; Arruda, Eric P.; Agarwal, Pooja; Kim, Kyoung-Han; Zhu, Yonghong; Zhu, Wei; Lebel, Melanie; Cheng, Chi Wa; Park, Chong Y.; Pierce, Stephanie A.; Guerchicoff, Alejandra; Pollevick, Guido D.; Chan, Toby Y.; Kabir, M. Golam; Cheng, Shuk Han; Husain, Mansoor; Antzelevitch, Charles; Srivastava, Deepak; Gross, Gil J.; Hui, Chi-Chung; Backx, Peter H.; Bruneau, Benoit G.

In: Cell, Vol. 123, No. 2, 21.10.2005, p. 347-358.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review