Iroquois homeobox gene 3 establishes fast conduction in the cardiac His-Purkinje network.

Abstract:

:Rapid electrical conduction in the His-Purkinje system tightly controls spatiotemporal activation of the ventricles. Although recent work has shed much light on the regulation of early specification and morphogenesis of the His-Purkinje system, less is known about how transcriptional regulation establishes impulse conduction properties of the constituent cells. Here we show that Iroquois homeobox gene 3 (Irx3) is critical for efficient conduction in this specialized tissue by antithetically regulating two gap junction-forming connexins (Cxs). Loss of Irx3 resulted in disruption of the rapid coordinated spread of ventricular excitation, reduced levels of Cx40, and ectopic Cx43 expression in the proximal bundle branches. Irx3 directly represses Cx43 transcription and indirectly activates Cx40 transcription. Our results reveal a critical role for Irx3 in the precise regulation of intercellular gap junction coupling and impulse propagation in the heart.

authors

Zhang SS,Kim KH,Rosen A,Smyth JW,Sakuma R,Delgado-Olguín P,Davis M,Chi NC,Puviindran V,Gaborit N,Sukonnik T,Wylie JN,Brand-Arzamendi K,Farman GP,Kim J,Rose RA,Marsden PA,Zhu Y,Zhou YQ,Miquerol L,Henkelman RM,Sta

doi

10.1073/pnas.1106911108

subject

Has Abstract

pub_date

2011-08-16 00:00:00

pages

13576-81

issue

33

eissn

0027-8424

issn

1091-6490

pii

1106911108

journal_volume

108

pub_type

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