Figure 5.

KID syndrome mutations produce functional HCs, but with differential effects on regulation by Ca²⁺ and pH and permeability to Ca²⁺. (A) Representative currents elicited by a series of voltage steps (10-s steps from +60 to −100 mV in intervals of 10 mV followed by a 5-s step to −110 mV) applied to oocytes expressing WT Cx26, A40V, G45E and D50N. Oocytes were voltage clamped to −20 mV. Currents shown in each case are from the same oocyte exposed to 0.2 and 2.0 mM Ca²⁺. WT Cx26, A40V, and G45E all showed substantial reductions in current magnitude in 2 mM Ca²⁺, whereas D50N was nearly insensitive to Ca²⁺. A large transient inward Ca²⁺-activated Cl current developed in oocytes expressing G45E when the voltage was stepped to −110 mV after depolarizing steps that activated these HCs (arrow). This was due to increased Ca²⁺ entry through G45E HCs. Data from (Sanchez et al., 2013). (B) Ca²⁺ activated Cl⁻ current plotted as a function of the macroscopic conductances of WT (black circles), G45E (red circles) and D50N (green circles) HCs in Xenopus oocytes. Solid lines correspond to regression lines fit to the data (best fit with a single exponential function). Inset: expanded view highlighting that only G45E induces Cl⁻ currents at considerably lower HC conductance values. Adapted from (Sánchez et al., 2010). (C) Bar graph showing the percent remaining HC current at pH 7.1 relative to a maximum at pH 8.0 (I_{pH 7.1}/I_{pH 8.0}). Currents were measured at a holding potential of −40 mV. Adapted from (Sanchez et al., 2014). Each bar represents the mean ratio ± SE. n = 5 for WT Cx26, 5 for A40V, 5 for G45E, and 5 for D50N.