KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology

Abstract

Human cloned KCNQ4 channels were stably expressed in HEK-293 cells and characterized with respect to function and pharmacology. Patch-clamp measurements showed that the KCNQ4 channels conducted slowly activating currents at potentials more positive than −60 mV. From the Boltzmann function fitted to the activation curve, a half-activation potential of −32 mV and an equivalent gating charge of 1.4 elementary charges was determined. The instantaneous current-voltage relationship revealed strong inward rectification. The KCNQ4 channels were blocked in a voltage-independent manner by the memory-enhancing M current blockers XE-991 and linopirdine with IC₅₀ values of 5.5 and 14 μM, respectively. The antiarrhythmic KCNQ1 channel blocker bepridil inhibited KCNQ4 with an IC₅₀ value of 9.4 μM, whereas clofilium was without significant effect at 100 μM. The KCNQ4-expressing cells exhibited average resting membrane potentials of −56 mV in contrast to −12 mV recorded in the nontransfected cells. In conclusion, the activation and pharmacology of KCNQ4 channels resemble those of M currents, and it is likely that the function of the KCNQ4 channel is to regulate the subthreshold electrical activity of excitable cells.