Fig. 9.

Gating of lens gap junction channels. A: gating of gap junctions in WT lenses. When current is injected into a central fiber cell and voltage recorded in DF, the series resistance (R_S in Fig. 6B) increases dramatically and reversibly when the lens is superfused with CO₂ solution, indicating closure of DF gap junction channels. In contrast, when voltage is recorded in MF, the increase in series resistance is relatively small, indicating MF channels are not closing and the small increase is due to closure of DF channels. [From Martinez-Wittingham et al. (127), with permission from the Association for Research in Vision and Ophthalmology.] B: gating of DF gap junction channels in WT and Cx50−/− lenses. KO of Cx50 reduces DF coupling conductance to about half its normal value, but the remaining Cx46 channels have lost most of their pH sensitivity. Because the KO lenses were in such poor condition, we thought the lack of gating might be an indirect effect, but this was ruled out by the data in C. [Redrawn from Baldo et al. (8).] C: gating of DF gap junction channels in WT and mefloquine-treated lenses. Mefloquine (MFQ) blocks gap junction coupling conductance in channels made from Cx50 but not Cx46. DF gap junction coupling conductance drops to about half its normal value over a period of ~ 1 h in MFQ, suggesting blockade of all Cx50 channels, leaving Cx46 channels to provide coupling. When the MFQ lenses are superfused with CO₂-containing solution, there is no closure of the remaining Cx46 channels, whereas in the untreated lens, both Cx50 and Cx50 channels close. The MFQ-treated lens was perfectly healthy, so the small residual gating seen in Cx50−/− lenses is actually due to their poor health, and in a healthy lens Cx46 channels are totally insensitive to pH. [From Martinez-Wittingham et al. (128), with permission from Springer Science + Business Media.]