Abstract
Heterotetramers of two kinds of KCNQ subunits form voltage-dependent K channels called M channels in the brain neurons. The outward current from M channels repolarizes the action potential. It is reported that point mutations in KCNQ3 cause a neuronal channelopathy. In this study, we primarily examined the functional consequences by mutations. Whole-cell currents were measured from the mutant KCNQ3 channels expressed in HEK293 cells. 1-1) Homomeric channels composed of mutant KCNQ3 lacked currents. 1-2) Heteromeric channels composed of wild-type KCNQ2 and mutant KCNQ3, which were mimicked to the native M channels, were lower in conductance than those composed of wild-type KCNQ2 and wild-type KCNQ3. 1-3) The activation curve of heteromeric channels composed of wild-type KCNQ2 and mutant KCNQ3 was shifted to the right than that composed of wild-type KCNQ2 and wild-type KCNQ3. We also reconstituted the three-dimensional protein structure of the mutant K channels. 2-1) The selectivity filter of wild-type KCNQ3 channel was structurally supported by chemical bonds. 2-2) The mutation, however, lead to a loss of chemical bonds. Such a structural alteration may result in the lower conductance in mutant KCNQ3 channels. [J Physiol Sci. 2006;56 Suppl:S80]
