SPATIAL DIFFERENCES IN GAP JUNCTION GATING IN THE LENS ARE A CONSEQUENCE OF CONNEXIN CLEAVAGE

Gap junctions in the vertebrate lens exhibit spatial differences in pH gating: those in the cortical fibre cells close upon tissue acidifica tion while those in the core region do not. It has been speculated tha t this difference in channel gating is a consequence of the cleavage o f the connexins (Cx) that form the gap junction channels. We report th e construction of a truncation mutant of ovine Cx50 which mimicks the cleavage in the intact lens. The construct when expressed in Xenopus o ocytes results in the formation of functional channels. Comparison wit h full-length Cx50 revealed a significant reduction in the pH sensitiv ity of the truncated form. This is the first evidence linking the non- uniform gating of gap junction channels in the lens with connexin clea vage. It also reveals how fibre cells in the core region remain connec ted despite the acidic environment caused by elevated lactate levels.