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Biophys. J. BioFAST: First Published December 22, 2006. doi:10.1529/biophysj.106.099358
© 2006 by the Biophysical Society.

A more recent version of this article appeared on March 15, 2007.
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Mindaugas Rackauskas
Maria M Kreuzberg
Mindaugas Pranevicius
Klaus Willecke
Vytas K. Verselis
Feliksas F Bukauskas
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CHANNELS, RECEPTORS, AND ELECTRICAL SIGNALING

Gating properties of heterotypic gap junction channels formed of connexins 40, 43 and 45

Mindaugas Rackauskas 1, Maria M Kreuzberg 2, Mindaugas Pranevicius 1, Klaus Willecke 2, Vytas K. Verselis 3 and Feliksas F Bukauskas 1*

1 Albert Einstein College of Medicine
2 Universitaet Bonn, Germany
3 Albert Einstein College of Med.

* To whom correspondence should be addressed. E-mail: fbukausk{at}aecom.yu.edu.

Submitted on October 11, 2006
Revised on November 16, 2006
Accepted on 4 December 2006


  Abstract
Connexins (Cxs) 40, 43 and 45 are expressed in many different tissues, but most abundantly in the heart, blood vessels and the nervous system. We examined formation and gating properties of heterotypic gap junction (GJ) channels assembled between cells expressing wild type Cx40, Cx43 or Cx45 and their fusion forms tagged with color variants of green fluorescent protein. We show that these Cxs, with exception of Cxs 40 and 43, are compatible to form functional heterotypic GJ channels. Cx40 and Cx43 hemichannels are unable or effectively impaired in their ability to dock and/or assemble into junctional plaques (JPs). When cells expressing Cx45 contacted those expressing Cx40 or Cx43 they readily formed JPs with cell-cell coupling characterized by asymmetric junctional conductance dependence on transjunctional voltage, Vj. We show that Cx40/Cx45 heterotypic GJ channels preferentially exhibit Vj-dependent gating transitions between open and residual states with a conductance of ~42 pS; transitions between fully open and closed states with conductance of ~52 pS in magnitude occur at substantially lower (~10-fold) frequency. Cx40/Cx45 junctions demonstrate electrical signal transfer asymmetry that can be modulated between unidirectional and bidirectional by small changes in the difference between holding potentials of the coupled cells. Furthermore, we demonstrate that both fast and slow gating mechanisms of Cx40 exhibit a negative gating polarity.

Key Words: Connexins, Cx40, Cx43, Cx45, Gap junctions, Voltge gating




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Copyright © 2006 by the Biophysical Society.