Gap junctional hemichannels in the heart

Abstract

Upon contacting each other, cells form gap junctions, in which each cell contributes half of the channel linking their cytoplasms, enabling them to share their metabolome up to a molecular weight of 1000. Each hemichannel (or connexon) is randomly inserted into the plasma membrane and then migrates to the site of cell-to-cell contact before pairing with the neighbouring cell's hemichannel to form a communicating conduit. This review summarizes the evidence for hemichannels in heart ventricular myocytes. Morphological findings are summarized describing how hemichannels are inserted into the plasma membrane. Once in the plasma membrane, hemichannels can be functionally detected electrophysiologically or by dye uptake assays. Each technique reveals specific aspects of hemichannel function. Using dye uptake studies, it is possible to investigate the biological regulation of hemichannels in vivo. Evidence is summarized which indicates that hemichannels are normally kept closed in the presence of normal extracellular Ca because they are phosphorylated at residues in the C-terminus regulated by the MAPK signalling pathway. When hemichannels are dephosphorylated, the channels open and allow dye uptake into the cells, as well as potentially deleterious ion exchange. Biological stresses, such as hyperosmolarity and metabolic inhibition, open hemichannels by this mechanism through activating phosphatases. The resulting ion fluxes may have important roles in heart physiology and pathophysiology.