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Dysfunction of Delayed Rectifier Potassium Channels in an Inherited Cardiac Arrhythmi a
Author(s) -
SANGUINETTI MICHAEL C.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb11302.x
Subject(s) - potassium , potassium channel , cardiology , inward rectifier potassium ion channel , medicine , chemistry , ion channel , receptor , organic chemistry
The rapid (l Kr ) and slow (I Ks ) delayed rectifier K + currents are key regulators of cardiac repolarization. HERG encodes the K r channel, and KVLQT1 and hminK encode subunits that coassemble to form K s channels. Mutations in any one of these genes cause Romano‐Ward syndrome, an autosomal dominant form of long QT syndrome (LQT). Mutations in KVLQT1 and HERG are the most common cause of LQT. Not all missense mutations of HERG or KVLQT1 have the same effect on K + channel function. Most mutations result in a dominant‐negative effect, but the severity of the resulting phenotype varies widely, as judged by reduction of current induced by coexpression of wild‐type and mutant subunits in heterologous expression systems. Mutations in hminK (S74L, D76N) reduce I Ks by shifting the voltage dependence of activation and accelerating channel deactivation. A recessive form of LQT is caused by mutations in either KVLQT1 or hminK . The functional consequences of mutations in delayed rectifier K + channel subunits are delayed cardiac repolarization, lengthened QT interval, and an increased risk of torsade de pointes and sudden death.