Article
- The EMBO Journal (2006) 25, 34 - 44
- doi:10.1038/sj.emboj.7600908
Published online: 8 December 2005
Subject Categories:
Intracellular calcium changes trigger connexin 32 hemichannel opening
Elke De Vuyst1, Elke Decrock1, Liesbet Cabooter1, George R Dubyak2, Christian C Naus3, W Howard Evans4 and Luc Leybaert1
- Department of Physiology and Pathophysiology, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
- Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
- Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff, UK
Correspondence to:
Luc Leybaert, Department of Physiology and Pathophysiology, Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185 (Block B, Room 306), 9000 Ghent, Belgium. Tel.: +32 9 240 33 66; Fax: +32 9 240 30 59; E-mail: Luc.Leybaert@ugent.be
Received 26 May 2005; Accepted 17 November 2005
Abstract
Connexin hemichannels have been proposed as a diffusion pathway for the release of extracellular messengers like ATP and others, based on connexin expression models and inhibition by gap junction blockers. Hemichannels are opened by various experimental stimuli, but the physiological intracellular triggers are currently not known. We investigated the hypothesis that an increase of cytoplasmic calcium concentration ([Ca2+]i) triggers hemichannel opening, making use of peptides that are identical to a short amino-acid sequence on the connexin subunit to specifically block hemichannels, but not gap junction channels. Our work performed on connexin 32 (Cx32)-expressing cells showed that an increase in [Ca2+]i triggers ATP release and dye uptake that is dependent on Cx32 expression, blocked by Cx32 (but not Cx43) mimetic peptides and a calmodulin antagonist, and critically dependent on [Ca2+]i elevation within a window situated around 500 nM. Our results indicate that [Ca2+]i elevation triggers hemichannel opening, and suggest that these channels are under physiological control.
Keywords:
- connexin mimetic peptides,
- exocytosis,
- P2X7 pores,
- purinergic receptors,
- vesicular release
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