The KCNQ5 potassium channel from mouse: A broadly expressed M-current like potassium channel modulated by zinc, pH, and volume changes

• Published in: Brain research. Molecular brain research. Vol. 139; no. 1; pp. 52 - 62
• Main Authors: Jensen, Henrik Sindal, Callø, Kirstine, Jespersen, Thomas, Jensen, Bo Skaaning, Olesen, Søren-Peter
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 13.09.2005; Elsevier
• Subjects: Animals; Biological and medical sciences; Cell Size; Cloning, Molecular; Fundamental and applied biological sciences. Psychology; Humans; Hydrogen-Ion Concentration; KCNQ Potassium Channels - genetics; KCNQ Potassium Channels - metabolism; KCNQ5; Kv7.5; Mice; Molecular Sequence Data; Oocytes - physiology; Patch-Clamp Techniques; Real-time RT PCR; Retigabine; RNA, Messenger - metabolism; Sequence Alignment; Tissue Distribution; Vertebrates: nervous system and sense organs; Volume regulation; Xenopus; Xenopus laevis; Zinc; Zinc - metabolism; Excitable membranes and synaptic transmission; Volume regulation; Kv7.5; Retigabine; Real-time RT PCR; pH; KCNQ5; Zinc; Rodentia; Ionic channel; Ionic current; Polymerase chain reaction; Vertebrata; Mammalia; Mouse; Animal; Potassium
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/j.molbrainres.2005.05.007

The KCNQ proteins compose a sub-group of the voltage-activated potassium channel family. The family consists of five members (KCNQ1 to 5—also named Kv7.1 to Kv7.5) encoded by single genes, which all give rise to proteins forming slowly activating potassium-selective ion channels. The physiological importance of the KCNQ channel family is emphasized by the fact that mutations in four of the five genes have been linked to human pathologies (KCNQ1 to 4). Here, we present the cloning and characterization of a novel KCNQ5 ortholog from mouse isolated by homology cloning from total mouse brain RNA (GenBank accession number: AY679158). The predicted protein is 95% identical to human KCNQ5. Upon expression in Xenopus oocytes, these proteins form voltage-dependent slowly activating channels with half-maximal activation at −21 mV. Our functional characterization revealed three novel modes of modulation: pH-dependent potentiation by Zn 2+ (EC 50 = 21.8 μM at pH 7.4), inhibition by acidification (IC 50 = 0.75 μM; pKa = 6.1), and regulation by small changes in cell volume. Furthermore, the channels are activated by the anti-convulsant drug retigabine (EC 50 = 2.0 μM) and inhibited by the M-current blockers linopiridine and XE-991. Finally, real-time RT-PCR was used to quantify the expression profile in a wide range of mouse tissues. These experiments revealed a relatively broad expression pattern in the nervous system but also expression in other tissues. Highest overall expression levels were observed in cortex and hippocampus. This study shows that murine KCNQ5 channels, in addition to sharing biophysical and pharmacological characteristics with the human ortholog, are tightly regulated by physiological stimuli such as changes in extracellular Zn 2+, pH, and tonicity, thus adding to the complex regulation of these channels.