Functional Expression of Two KvLQT1-related Potassium Channels Responsible for an Inherited Idiopathic Epilepsy

• Published in: The Journal of biological chemistry Vol. 273; no. 31; pp. 19419 - 19423
• Main Authors: Yang, Wen-Pin, Levesque, Paul C., Little, Wayne A., Conder, Mary Lee, Ramakrishnan, Pankajavalli, Neubauer, Michael G., Blanar, Michael A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31-07-1998; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Brain - metabolism; Cloning, Molecular; Electrophysiology; Epilepsy, Generalized - genetics; Gene Expression Regulation - genetics; Humans; Ion Channel Gating - physiology; KCNQ Potassium Channels; KCNQ1 Potassium Channel; KCNQ2 Potassium Channel; KCNQ3 Potassium Channel; Microinjections; Oocytes - physiology; Potassium Channels - genetics; Potassium Channels - metabolism; Potassium Channels - physiology; Potassium Channels, Voltage-Gated; RNA, Messenger - metabolism; Xenopus
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.31.19419

Benign familial neonatal convulsions (BFNC), a class of idiopathic generalized epilepsy, is an autosomal dominantly inherited disorder of newborns. BFNC has been linked to mutations in two putative K+ channel genes, KCNQ2 andKCNQ3. Amino acid sequence comparison reveals that both genes share strong homology to KvLQT1, the potassium channel encoded byKCNQ1, which is responsible for over 50% of inherited long QT syndrome. Here we describe the cloning, functional expression, and characterization of K+ channels encoded byKCNQ2 and KCNQ3 cDNAs. Individually, expression of KCNQ2 or KCNQ3 in Xenopus oocytes elicits voltage-gated, rapidly activating K+-selective currents similar to KCNQ1. However, unlike KCNQ1, KCNQ2 and KCNQ3 currents are not augmented by coexpression with the KCNQ1 β subunit, KCNE1 (minK, IsK). Northern blot analyses reveal that KCNQ2 andKCNQ3 exhibit similar expression patterns in different regions within the brain. Interestingly, coexpression of KCNQ2 and KCNQ3 results in a substantial synergistic increase in current amplitude. Coexpression of KCNE1 with the two channels strongly suppressed current amplitude and slowed kinetics of activation. The pharmacological and biophysical properties of the K+currents observed in the coinjected oocytes differ somewhat from those observed after injecting either KCNQ2 or KCNQ3 by itself. The functional interaction between KCNQ2 and KCNQ3 provides a framework for understanding how mutations in either channel can cause a form of idiopathic generalized epilepsy.