Voltage gating of gap junctions in cochlear supporting cells: Evidence fornonhomotypic channels

The organ of Corti has been found to have multiple gap junction subunits, c onnexins, which are localized solely in nonsensory supporting cells. Connex in mutations can induce sensorineural deafness. However, the characteristic s and functions of inner ear gap junctions are not well known. In the prese nt study, the voltage-dependence of gap junctional conductance (G(j)) in co chlear supporting cells was examined by the double voltage clamp technique. Multiple types of asymmetric voltage dependencies were found for both nonj unctional membrane voltage (V-m) and transjunctional (V-j) voltage. Respons es for each type of voltage dependence were categorized into four groups. T he first two groups showed rectification that was polarity dependent. The t hird group exhibited rectification with either voltage polarity, i.e., thes e cells possessed a bell-shaped G(j)-V-j or G(j)-V-m function. The rectific ation due to V-j had fast and J slow components. On the other hand, V-m-dep endent gating was fast (<5 msec), but stable. Finally, a group was found th at evidenced no voltage dependence, although the absence of V-j dependence did not prelude V-m dependence ni and vice versa. In fact, for all groups V -j sensitivity could be independent of V-m sensitivity. The data show that most gap junctional channels in the inner ear have asymmetric voltage gatin g, which is indicative of heterogeneous coupling and may result from hetero typic channels or possibly heteromeric configurations. This heterogeneous c oupling implies that single connexin gene mutations may affect the normal p hysiological function of gap junctions that are not limited to homotypic co nfigurations.