title: Cx43-hemichannel function and regulation in physiology and pathophysiology: insights from the bovine corneal endothelial cell system and beyond.
abstract: Intercellular communication in primary bovine corneal endothelial cells (BCECs) is mainly driven by the release of extracellular ATP through Cx43 hemichannels. Studying the characteristics of Ca(2+)-wave propagation in BCECs, an important form of intercellular communication, in response to physiological signaling events has led to the discovery of important insights in the functional properties and regulation of native Cx43 hemichannels. Together with ectopic expression models for Cx43 hemichannels and truncated/mutated Cx43 versions, it became very clear that loop/tail interactions play a key role in controlling the activity of Cx43 hemichannels. Interestingly, the negative regulation of Cx43 hemichannels by enhanced actin/myosin contractility seems to impinge upon loss of these loop/tail interactions essential for opening Cx43 hemichannels. Finally, these molecular insights have spurred the development of novel peptide tools that can selectively inhibit Cx43 hemichannels, but neither Cx43 gap junctions nor hemichannels formed by other Cx isoforms. These tools now set the stage to hunt for novel physiological functions for Cx43 hemichannels in primary cells and tissues and to tackle disease conditions associated with excessive, pathological Cx43-hemichannel openings.
authors.affiliation: Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven Leuven, Belgium.
authors.forename: Catheleyne
authors.initials: C
authors.lastname: D'hondt
authors.affiliation: Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven Leuven, Belgium.
authors.forename: Jegan
authors.initials: J
authors.lastname: Iyyathurai
authors.affiliation: Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven Leuven, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Himpens
authors.affiliation: Physiology Group, Department of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University Ghent, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Leybaert
authors.affiliation: Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven Leuven, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Bultynck
keywords: actin/myosin contractility; corneal endothelial cells; hemichannels; intercellular communication; loop/tail interactions; selective inhibition of Cx43 hemichannels