Connexin hemichannel mediated ephaptic inhibition in the retina.

Connexins are the building blocks of gap-junctions; sign conserving electrical synapses. Recently it has been shown that connexins can also function as hemichannels and can mediate a sign inverting inhibitory synaptic signal from horizontal cells to cones via an ephaptic mechanism. In this review we will discuss the critical requirements for such an ephaptic interaction and relate these to the available experimental evidence. The highly conserved morphological structure of the cone synapse together with a number of specific connexin proteins and proteoglycans present in the synaptic complex of the cones creates a synaptic environment that allows ephaptic interactions. The connexins involved are members of a special group of connexins, encoded by the GJA9 and GJA10 genes. Surprisingly, in contrast to many other vertebrates, mouse and other rodents seem to lack a GJA9 encoded connexin. The specific combination of substances that block feedback and the highly specific modification of feedback in a zebrafish lacking Cx55.5 hemichannels all point to an ephaptic feedback mechanism from horizontal cells to cones. This article is part of a Special Issue entitled Electrical Synapses.