The voltage gates of connexin channels are sensitive to CO(2).

Cx45 channel sensitivity to CO(2), transjunctional voltage (V(j)) and inhibition of calmodulin (CaM) expression was tested in oocytes by dual voltage-clamp. Cx45 channels are very sensitive to V(j) and close preferentially by the slow gate, likely the same as the chemical gate. With CO(2)-induced drop in junctional conductance (G(j)), the speed of V(j)-dependent inactivation of junctional current (I(j)) and V(j) sensitivity increased. With 40 mV V(j), the tau of single exponential I(j) decay reversibly decreased by approximately 40% with CO(2), and G(j steady state)/G(j peak) decreased multiphasically, indicating that kinetics and V(j) sensitivity of chemical/slow-V(j) gating are altered by changes in [H(+)](i) and/or [Ca(2+)](i). With 15 min exposure to CO(2), G(j) dropped to 0% in controls and by approximately 17% following CaM expression inhibition; similarly, V(j) sensitivity decreased significantly. This indicates that the speed and sensitivity of V(j)-dependent inactivation of Cx45 channels are increased by CO(2), and that CaM plays a role in gating. Cx32 channels behaved similarly, but the drop in both G(j steady state)/G(j peak) and tau with CO(2) matched more closely that of G(j peak). In contrast, sensitivity and speed of V(j) gating of Cx40 and Cx26 channels decreased, rather than increased, with CO(2) application.