This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Glatter, K. A. Articles by Chiamvimonvat, N. Search for Related Content PubMed PubMed Citation Articles by Glatter, K. A. Articles by Chiamvimonvat, N. Related Collections Arrythmias-basic studies Quantitative modeling

(Circulation Research. 2003;92:941.)
© 2003 American Heart Association, Inc.

Editorials

Tachy- or Bradyarrhythmias

Implications for Therapeutic Intervention in LQT3 Families

Kathryn A. Glatter, Nipavan Chiamvimonvat

From the Division of Cardiovascular Medicine (K.A.G., N.C.), University of California, Davis, Davis, Calif; Department of Veterans Affairs (N.C.), Northern California Health Care System, Mather, Calif.

Correspondence to Nipavan Chiamvimonvat, Division of Cardiovascular Medicine, University of California, Davis, One Shields Ave, TB 172, Davis, CA 95616. E-mail nchiamvimonvat@ucdavis.edu

Key Words: long-QT syndrome • Na⁺ currents • SCN5A • sinus node dysfunction

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Congenital long-QT syndrome (LQTS) is a group of inherited disorders that is associated with a prolonged QT interval on the ECG. It can be associated with syncope and sudden death due to episodic cardiac arrhythmias, particularly torsades de pointes and ventricular fibrillation. One common familial form is inherited as an autosomal dominant trait (the Romano-Ward syndrome). Much progress toward understanding the molecular mechanisms in congenital LQTS has been made over the past 8 years. Mutations in several ion channel genes have been discovered in different families with LQTS: KVLQT1, HERG, SCN5A, minK, MiRP1^1–5 (for review see⁶). Indeed, these studies provided the first molecular basis into the pathogenesis of cardiac arrhythmias and, importantly, possible new insights into the more common types of acquired LQTS such as cardiomyopathy, ischemia, as well as drug-induced LQTS.⁷

SCN5A, located on chromosome 3p21-24, encodes the subunit of cardiac Na⁺ channels.⁸ Mutation analyses have revealed 30 distinct mutations of SCN5A associated with LQTS type 3 (LQT3).⁹ Mutations of KVLQT1, a gene that encodes for a slowly activating delayed rectifier K⁺ channel (I_Ks), cause LQT1, the most common form of LQTS.¹ Mutations in the minK gene cause LQT5.⁴ Mutations in HERG have been linked to LQT2³ and represent 45% of the known LQTS defects. This gene encodes subunits that form cardiac I_Kr, a rapidly activating delayed-rectifier K⁺ channel. MiRP1, or minK-related protein 1, putatively coassembles with HERG subunits to form cardiac I_Kr channels and has been . . . [Full Text of this Article]