Hemichannel composition and electrical synaptic transmission: molecular diversity and its implications for electrical rectification

© The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Frontiers in Cellular Neuroscience 8 (2014): 324, doi:10.3389/fncel.2014.00324.Unapposed hemichannels (HCs) formed by hexamers of gap junction proteins are now known to be involved in various cellular processes under both physiological and pathological conditions. On the other hand, less is known regarding how differences in the molecular composition of HCs impact electrical synaptic transmission between neurons when they form intercellular heterotypic gap junctions (GJs). Here we review data indicating that molecular differences between apposed HCs at electrical synapses are generally associated with rectification of electrical transmission. Furthermore, this association has been observed at both innexin and connexin (Cx) based electrical synapses. We discuss the possible molecular mechanisms underlying electrical rectification, as well as the potential contribution of intracellular soluble factors to this phenomenon. We conclude that asymmetries in molecular composition and sensitivity to cellular factors of each contributing hemichannel can profoundly influence the transmission of electrical signals, endowing electrical synapses with more complex functional properties.Supported by the Grass Foundation, a Howard Hughes Medical Institute International Student Research Fellowship to Nicolás Palacios-Prado, a Marie-Curie Zukunfts-kolleg Incoming Fellowship to Wolf Huetteroth, and National Institutes of Health grants NIH DC03186, DC011099, NS055726, NS085772 and NS0552827 to Alberto E. Pereda