Biological role of connexin intercellular channels and hemichannels

Abstract

Gap junctions (GJ) and hemichannels (HC) formed from the protein subunits called connexins are transmembrane conduits for the exchange of small molecules and ions. Connexins and another group of HC-forming proteins, pannexins comprise the two families of transmembrane proteins ubiquitously distributed in vertebrates. Most cell types express more than one connexin or pannexin. While connexin expression and channel activity may vary as a function of physiological and pathological states of the cell and tissue, only a few studies suggest the involvement of pannexin HC in acquired pathological conditions. Importantly, genetic mutations in connexin appear to interfere with GJ and HC function which results in several diseases. Thus connexins could serve as potential drug target for therapeutic intervention. Growing evidence suggests that diseases resulting from HC dysfunction might open a new direction for development of specific HC reagents. This review provides a comprehensive overview of the current studies of GJ and HC formed by connexins and pannexins in various tissue and organ systems including heart, central nervous system, kidney, mammary glands, ovary, testis, lens, retina, inner ear, bone, cartilage, lung and liver. In addition, present knowledge of the role of GJ and HC in cell cycle progression, carcinogenesis and stem cell development is also discussed.

Fig. 1. Gap junctions and hemichannels formed by the protein subunits, connexins play diverse roles in various organs and tissues

The top panel shows the role of connexins in regulating cell death, differentiation and overall survival of several organ systems. The middle panel describes the involvement of gap junction channels in ionic conduction, metabolic coupling and passage of second messengers in the different organ systems. The bottom panel summarizes the present knowledge of the role of hemichannels in regulating ionic conduction and overall response of cells of various organs to extracellular signaling, injury, ischemic preconditioning and mechanical stimulation.