KvLQT1, a voltage-gated potassium channel responsible for human cardiac arrhythmias

Abstract

The clinical features of long QT syndrome result from episodic life-threatening cardiac arrhythmias, specifically the polymorphic ventricular tachycardia torsades de pointes. KVLQT1 has been established as the human chromosome 11-linked gene responsible for more than 50% of inherited long QT syndrome. Here we describe the cloning of a full-length KVLQT1 cDNA and its functional expression. KVLQT1 encodes a 676-amino acid polypeptide with structural characteristics similar to voltage-gated potassium channels. Expression of KvLQT1 in Xenopus oocytes and in human embryonic kidney cells elicits a rapidly activating, K ؉ -selective outward current. The I Kr -specific blockers, E-4031 and dofetilide, do not inhibit KvLQT1, whereas clofilium, a class III antiarrhythmic agent with the propensity to induce torsades de pointes, substantially inhibits the current. Elevation of cAMP levels in oocytes nearly doubles the amplitude of KvLQT1 currents. Coexpression of minK with KvLQT1 results in a conductance with pharmacological and biophysical properties more similar to I Ks than other known delayed rectifier K ؉ currents in the heart.

Sevoflurane Inhibition of the Slowly Activating Delayed Rectifier K+ Current in Guinea Pig Ventricular Cells

“…However, little is known about whether delayed rectifier K + currents, which are sensitive to volatile anesthetics, is present in the central nervous system. It has been reported that KVLQT1 is strongly expressed in human heart and pancreas (32), and KCNE1 mRNA is abundant in the kidney, submandibular gland, and the uterus (33,34). However, both are hardly expressed in the brain.…”

Anxiolytic Effects of Maxipost (BMS-204352) and Retigabine via Activation of Neuronal Kv7 Channels

“…There are five known ␣-subunits (K v 7.1-K v 7.5), and the sequence alignment of the hydrophobic regions divides them into two groups, one comprising K v 7.1 and the other K v 7.2 to K v 7.5. K v 7.1 is found in the heart (Yang et al, 1997) and in epithelial tissues (Schroeder et al, 2000b), whereas K v 7.2 to K v 7.5 are expressed primarily in neurons and are therefore collectively referred to as neuronal (Biervert et al, 1998;Singh et al, 1998;Yang et al, 1998;Kharkovets et al, 2000). All K v 7 channels, with the exception of K v 7.5, have been linked with hereditary diseases: K v 7.1 with cardiac long QT syndrome, K v 7.2 and K v 7.3 with benign neonatal familial convulsions, and K v 7.4 with deafness (for reviews, see Robbins, 2001;Gribkoff, 2003).…”

Molecular Cloning and Functional Expression of KCNQ5, a Potassium Channel Subunit That May Contribute to Neuronal M-current Diversity

“…Consistently, both channel proteins contain threonine residues within the pore region at a position that mainly determines sensitivity to external blockade by TEA. While in KCNQ2 a tyrosine residue at this position confers high TEA sensitivity (19,35), other residues may be responsible for the intermediate TEA sensitivity of KCNQ1 and KCNQ4 (6,34). Another nonspecific potassium channel blocker, quinidine, at 300 M blocked KCNQ5 currents by 50%.…”

“…So far, the KCNQ family consists of four members, all of which are associated with hereditary human diseases. KCNQ1 functionally interacts with KCNE1 (IsK) (2), a small ␤-subunit protein with a single transmembrane domain, to generate the slowly activating delayed rectifier I Ks current of cardiomyocytes (3)(4)(5)(6).…”