Original Article Regulation of cellular function by connexin hemichannels

Introduction Gap junctions (GJs) and hemichannels (HCs) are composed of proteins known as connexins which form a principal means of cell-cell com-munication in animal tissues, allowing the dif-fusion of ions, metabolites and secondary mes-sengers [1, 2]. Up to twenty one different con-nexins have been identified till now [3] and their nomenclature is based on the molecular weight; for example, connexin (Cx) 43 is a 43 kDa protein. Connexins oligomerize into hexameric connexons and docking of two such connexon channels expressed on adjacent cells lead to the construction of a GJ channel. Connexons formed by a single type of connexin are termed homomeric and channels with a mixture of two types of connexins are known as heteromeric channels [1, 4, 5]. Heterotypic channels are formed when two homomeric con-nexons formed by different connexins dock onto each other [6-8]. Formation of hetero-meric-heterotypic GJ channels is also reported [4, 9, 10]. Intermixing of connexins depends on their compatibility, for example, Cx43 cannot form heteromeric channels with Cx26 [11]. Such intermixing could confer special functions to GJ channels as they exhibit different perme-ability properties in comparison to homomeric-homotypic channels alone [12]. GJs and HCs allow passage of the molecules with a cut off weight of 1 kDa and the specific-ity depends on the type of connexin. The shape of the pore and the pore-lining residues of con-nexons contribute to the specificity of mole-cules that are exchanged [13]. Post-translational modifications, such as phos-phorylation and S-nitrosylation, also affect the molecular transfer through HCs [14, 15]. Therefore, intermixing of connexins and post-translational modifications could be critical in regulation of cell communication. Molecular exchange via connexin channels is thought to be essential for signal propagation in cells, and to be involved in growth control, differentia-tion, embryonic development and reproduc-tion [16, 17]. It has been technically challeng-ing to identify specific molecules that are com-municated through GJs formed by different connexins. However, identification of molecules passing through HCs is known to be less chal-lenging as factors released by HCs expressed in cell culture systems can be collected from Int J Biochem Mol Biol 2011;2(2):119-128 www.ijbmb.org /ISSN:2152-4114/IJBMB1102001