Co-expression of lens fiber connexins modifies hemi-gap-junctional channelbehavior

Lens fiber cells contain two gap junction proteins (Cx56 and Cx45.6 in the chicken). Biochemical studies have suggested that these two proteins can fo rm heteromeric connexons, To investigate the biophysical properties of hete romeric lens connexons, Cx56 was co-expressed with Cx45.6 (or its mouse cou nterpart, Cx50) in Xenopus oocytes, Whole-cell and single-channel currents were measured in single oocytes by conventional two-microelectrode voltage- clamp and patch clamp techniques, respectively. Injection of Cx56 cRNA indu ced a slowly activating, nonselective cation current that activated on depo larization to potentials higher than -10 mV. In contrast, little or no hemi channel current was induced by injection of Gx50 or Cx45.6 cRNA, Go-express ion of Gx56 with Gx45.6 or Cx50 led to a shift in the threshold for activat ion to -40 or -70 mV, respectively, It also slowed the rate of deactivation of the hemichannel currents. Moreover, an increase in the unitary conducta nce, steady state probability of hemichannel opening and mean open times at negative potentials, was observed in (Gx56 + Cx45.6) cRNA-injected oocytes compared with Cx56 cRNA-injected oocytes. These results indicate that coex pression of lens fiber connexins gives rise to novel channels that may be e xplained by the formation of heteromeric hemichannels that contain both con nexins.