Human KCNQ4/KCNQ5 Stable Cell Line-HEK293

Potassium ion channels are the most widely distributed of ion channels and are found in almost all living organisms. A typical voltage gated potassium ion channel has a tetrameric structure consisting of 4 protein subunits combining to form a central ion conducting pore across the cell membrane. Voltage gated ion channels open and close in response to changes in the transmembrane voltage. KCNQ genes encode Kv7 potassium channels that have been associated with both cardiac and hearing abnormalities in humans, most notably the KNCQ1 gene. Using a partial KCNQ3 cDNA Kubisch et al. screened a human retinal cDNA lambda phage library and obtained a novel homolog they named KCNQ4. When expressed in Xenopus oocytes KCNQ4 encodes potassium current (Kv7.4) inhibited by 30% in the presence of 200 μM linopirdine, whereas the current due to KCNQ3/KCNQ4 (Kv7.3/Kv7.4) heteromers in the same study was inhibited by 75% at that concentration. Schroeder et al. used a KCNQ3 cDNA probe to obtain a KCNQ fragment from a human thalamus cDNA library. Amplification & extension techniques subsequently yielded a full-length KCNQ5 (Kv7.5) gene. These authors also mapped the KCNQ5 gene to the 6q14 region of the human chromosome. Brueggemann et al. found that the inhibition of native potassium currents in A7r5 rat aortic smooth muscle cells by vasopressin was PKC-dependent, and the current amplitude was decreased when RNA interference techniques directed toward KCNQ5 were utilized. Rat middle cerebral arteries have an expression profile of KCNQ4>KCNQ5>KCNQ1 in the sarcolemmal membrane, and linopirdine enhances the myogenic response of the isolated arteries. Agents that open KCNQ channels reverse vasoconstriction, leading to the hypothesis that Kv7 channels could represent novel targets for treatment of cerebral vasospasm.