Dear Editor, I read with great interest the recent article by Saif et al1 in a recent issue of your esteemed journal. The article is highly thought provoking. Interestingly, the past few years have seen the identifi cation of a number of pathological conditions resulting because of mutations in the KCNQ1 gene. For instance, increased disease severity is seen in patients with Long QT syndrome (L...

KCNQ1 voltage-gated K(+) channels (Kv7.1) associate with the family of five KCNE peptides to form complexes with diverse gating properties and pharmacological sensitivities. The varied gating properties of the different KCNQ1-KCNE complexes enables the same K(+) channel to function in both excitable and non excitable tissues. Small molecule activators would be valuable tools for dissecting the ...

KCNQ1 channels assemble with KCNE1 transmembrane (TM) peptides to form voltage-gated K(+) channel complexes with slow activation gate opening. The cytoplasmic C-terminal domain that abuts the KCNE1 TM segment has been implicated in regulating KCNQ1 gating, yet its interaction with KCNQ1 has not been described. Here, we identified a protein-protein interaction between the KCNE1 C-terminal domain...

The delayed rectifier I(Ks) potassium channel, formed by coassembly of α- (KCNQ1) and β- (KCNE1) subunits, is essential for cardiac function. Although KCNE1 is necessary to reproduce the functional properties of the native I(Ks) channel, the mechanism(s) through which KCNE1 modulates KCNQ1 is unknown. Here we report measurements of voltage sensor movements in KCNQ1 and KCNQ1/KCNE1 channels usin...

Voltage-gated KCNQ1 (Kv7.1) potassium channels are expressed abundantly in heart but they are also found in multiple other tissues. Differential coassembly with single transmembrane KCNE beta subunits in different cell types gives rise to a variety of biophysical properties, hence endowing distinct physiological roles for KCNQ1-KCNEx complexes. Mutations in either KCNQ1 or KCNE1 genes result in...

KCNQ1 encodes KCNQ1, which belongs to a family of voltage-dependent K(+) ion channel proteins. KCNQ1 associates with a regulatory subunit, KCNE1, to produce the cardiac repolarizing current, I(Ks). Loss-of-function mutations in the human KCNQ1 gene have been linked to Jervell and Lange-Nielsen Syndrome (JLNS), a disorder characterized by profound bilateral deafness and a cardiac phenotype. To g...

BACKGROUND KCNQ1 and KCNE1 assemble to form the slow delayed rectifier (IKs) channel critical for shortening ventricular action potentials during high β-adrenergic tone. However, too much IKs under basal conditions poses an arrhythmogenic risk. Our objective is to understand how adult ventricular myocytes regulate the IKs amplitudes under basal conditions and in response to stress. METHODS AN...

Voltage-gated potassium (Kv) channels extend their functional repertoire by coassembling with MinK-related peptides (MiRPs). MinK slows the activation of channels formed with KCNQ1 alpha subunits to generate the voltage-dependent I(Ks) channel in human heart; MiRP1 and MiRP2 remove the voltage dependence of KCNQ1 to generate potassium "leak" currents in gastrointestinal epithelia. Other Kv alph...

KCNQ1 (Kv7.1) is a unique member of the superfamily of voltage-gated K(+) channels in that it displays a remarkable range of gating behaviors tuned by coassembly with different β subunits of the KCNE family of proteins. To better understand the basis for the biophysical diversity of KCNQ1 channels, we here investigate the basis of KCNQ1 gating in the absence of β subunits using voltage-clamp fl...

Modulation of voltage-gated potassium (KV) channels by the KCNE family of single transmembrane proteins has physiological and pathophysiological importance. All five KCNE proteins (KCNE1-KCNE5) have been demonstrated to modulate heterologously expressed KCNQ1 (KV7.1) with diverse effects, making this channel a valuable experimental platform for elucidating structure-function relationships and m...