Jervell and Lange-Nielsen Syndrome: Pathophysiological Effects of Non-functional Iks Channels

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Introduction
Jervell and Lange-Nielsen Syndrome (JLNS) is a type of long QT syndrome that results in the delayed repolarization of cardiac myocytes, which is observed as an increase in the QT interval on an electrocardiogram (ECG), as well as congenital bilateral sensorineural deafness1, 5-8. This is due to homozygous or compound heterozygous mutations in either the KCNQ1 gene or the KCNE1 gene that result in the complete loss of function of the slowly activating delayed rectifier potassium channels (Iks) in cardiac muscle tissue and in the inner ear.1, 5-8 The structure and function of this channel will be considered with respect to the effects of mutations in KCNQ1 and KCNE1, the resulting pathophysiology and treatment of this disorder.
Structure and Function of the Iks Channel
The Iks channel is a voltage-gated channel that is responsible for the repolarization of cardiac myocytes as well as the maintenance of the endocochlear potential via K+ efflux1. This channel is encoded by two genes: KCNQ1 and KCNE11. The KCNQ1 gene encodes the α subunit of this channel, four of which combine to form a tetramer1. Each α subunit spans the membrane six times (Figure 1) - the first four segments allow the detection of voltage changes and the last two segments create a pore through which K+ can pass2. The β subunit encoded by the KCNE1 gene displays a single transmembrane portion and confers the characteristic properties of the Iks channel by associating with the pore portion of the tetramer2. To determine the stoichiometry of α subunits to β subunits, Nakajo and colleagues (2) injected RNA pertaining to KCNQ1 and KCNE1 into Xenopus laevis oocytes and examined the level of expression of each of these genes by fluorescently tagging the re...

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