KCNQ potassium channels: physiology, pathophysiology, and pharmacology

KCNQ genes encode a growing family of six transmembrane domains, single por t-loop, K+ channel alpha -subunits that have a wide range of physiological correlates. KCNQ 1 (KVLTQ 1) is co-assembled with the product of the KCNE 1 (minimal K (+) -channel protein) gene in the heart to form a cardiac-delay ed rectifier-like K+ current. Mutations in this channel can cause one form of inherited Long QT syndrome (LQT 1), as well as being associated with a f orm of deafness. KCNQ 1 can also co-assemble with KCNE3, and may be the mol ecular correlate of the cyclic AMP-regulated K+ current present in colonic crypt cells. KCNQ2 and KCNQ3 heteromultimers are thought to underlie the M- current; mutations in these genes may cause an inherited form of juvenile e pilepsy. The KCNQ4 gene is thought to encode the molecular correlate of the I-K.n in outer hair cells of the cochlea and I-K.L in Type I hair calls of the vestibular apparatus, mutations in which lead to a form of inherited d eafness. The recently identified KCNQ5 gene is expressed in brain and skele tal muscle. and can co-assemble with KCNQ3. suggesting it may also play a r ole in the M-current heterogeneity This review will set this family of K - channels amongst the other known families. It will highlight the genes, phy siology, pharmacology. and pathophysiology of this recently discovered, but important, family of K+ channels. (C) 2001 Elsevier Science Inc. All right s reserved.