Cx43-hemichannel function and regulation in physiology and pathophysiology: insights from the bovine corneal endothelial cell system and beyond

Frontiers in Physiology

Geert eBultynck¹  Catheleyne eD'hondt¹  Jegan eIyyathurai¹  Bernard eHimpens¹  Luc eLeybaert² 

[1] KULeuven;University Ghent;

关键词: intercellular communication;    hemichannels;    loop/tail interactions;    actin/myosin contractility;    selective inhibition of Cx43 hemichannels;    corneal endothelial cells;   

DOI  :  10.3389/fphys.2014.00348

来源: DOAJ

【 摘 要 】

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 Ca2+-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 not Cx43 gap junctions or 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.

【 授权许可】

Unknown