CO(2) sensitivity of voltage gating and gating polarity of gapjunction channels--connexin40 and its COOH-terminus-truncated mutant.

The CO(2) sensitivity of transjunctional voltage ( V(j)) gating was studied by dual voltage clamp in oocytes expressing mouse Cx40 or its COOH terminus (CT)-truncated mutant (Cx40-TR). V(j) sensitivity, determined by a standard V(j) protocol (20 mV V(j) steps, 120 mV maximal), decreased significantly with exposure to 30% CO(2). The Boltzmann values of control versus CO(2)-treated oocytes were: V(0) = 36.3 and 48.7 mV, n = 5.4 and 3.7, and G(j min) = 0.21 and 0.31, respectively. CO(2) also affected the kinetics of V(j)-dependent inactivation of junctional current ( I(j)); the time constants of two-term exponential I(j) decay, measured at V(j) = 60 mV, increased significantly with CO(2) application. Similar results were obtained with Cx40-TR, suggesting that CT does not play a role in this phenomenon. The sensitivity of Cx40 channels to 100% CO(2) was also unaffected by CT truncation. There is evidence that CO(2) decreases the V(j) sensitivity of Cx26, Cx50 and Cx37 as well, whereas it increases that of Cx45 and Cx32 channels. Since Cx40, Cx26, Cx50 and Cx37 gate at the positive side of V(j), whereas Cx45 and Cx32 gate at negative V(j), it is likely that V(j) behavior with respect to CO(2)-induced acidification varies depending on gating polarity, possibly involving the function of the postulated V(j) sensor (NH(2)-terminus).