Abstract
Cx45 channel sensitivity to CO2, transjunctional voltage (Vj) and inhibition of calmodulin (CaM) expression was tested in oocytes by dual voltage-clamp. Cx45 channels are very sensitive to Vjand close preferentially by the slow gate, likely the same as the chemical gate. With CO2-induced drop in junctional conductance (Gj), the speed of Vj-dependent inactivation of junctional current (Ij) and Vjsensitivity increased. With 40 mV Vj, the τ of single exponential Ijdecay reversibly decreased by ∼40% with CO2, and Gj steady state/Gj peakdecreased multiphasically, indicating that kinetics and Vjsensitivity of chemical/slow-Vjgating are altered by changes in [H+]iand/or [Ca2+]i. With 15 min exposure to CO2, Gjdropped to 0% in controls and by ∼17% following CaM expression inhibition; similarly, Vjsensitivity decreased significantly. This indicates that the speed and sensitivity of Vj-dependent inactivation of Cx45 channels are increased by CO2, and that CaM plays a role in gating. Cx32 channels behaved similarly, but the drop in both Gj steady state/Gj peakand τ with CO2matched more closely that of Gj peak. In contrast, sensitivity and speed of Vjgating of Cx40 and Cx26 channels decreased, rather than increased, with CO2application.