The KCNQ1 Potassium Channel: From Gene to Physiological Function

Jespersen, Thomas; Grunnet, Morten; Olesen, Søren‐Peter

doi:10.1152/physiol.00031.2005

Cited by 238 publications

(261 citation statements)

References 106 publications

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“…However, the transient kinetic property (fast activation and inactivation, Fig. 3B), is not consistent with the well-known slow kinetics of Kv7.1 (Jespersen et al, 2005). Because the primers for K + channels used in the present study did not cover all the members of Kv superfamily, the 4-AP-insensitive current might be encoded by one of the other Kv channels not analyzed yet.…”

Section: Discussionmentioning

confidence: 55%

Identification and Functional Characterization of Ion Channels in CD34+ Hematopoietic Stem Cells from Human Peripheral Blood

Park

Pang

Park

et al. 2011

Molecules and Cells

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Section: Discussionmentioning

confidence: 55%

Identification and Functional Characterization of Ion Channels in CD34+ Hematopoietic Stem Cells from Human Peripheral Blood

Park

Pang

Park

et al. 2011

Molecules and Cells

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“…9 KCNQ1 channel is distributed widely in epithelial and non-epithelial tissues throughout the body and regulates many key physiological functions such as maintaining the membrane potential as well as controlling the water and salt homeostasis. 10,11 Mutations of KCNQ1 have been confirmed to be responsible in most cases for the long QT syndrome, a genetic disorder characterized by increases in the cardiac action potential duration, therefore KCNQ1 was well known as KvLQT1 (Kv7.1). 9,12 In rodent pancreas, KCNQ1 has been demonstrated to be expressed in cells of islets of Langerhans.…”

Section: Introductionmentioning

confidence: 99%

Chromanol 293B, an inhibitor of KCNQ1 channels, enhances glucose-stimulated insulin secretion and increases glucagon-like peptide-1 level in mice

Liu

Wang

et al. 2014

Islets

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Glucose-stimulated insulin secretion (GSIS) is a highly regulated process involving complex interaction of multiple factors. Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) is a susceptibility gene for type 2 diabetes (T2D) and the risk alleles of the KCNQ1 gene appear to be associated with impaired insulin secretion. The role of KCNQ1 channel in insulin secretion has been explored by previous work in clonal pancreatic b-cells but has yet to be investigated in the context of primary islets as well as intact animals. Genetic studies suggest that altered incretin glucagon-like peptide-1 (GLP-1) secretion might be a potential link between KCNQ1 variants and impaired insulin secretion, but this hypothesis has not been verified so far. In the current study, we examined KCNQ1 expression in pancreas and intestine from normal mice and then investigated the effects of chromanol 293B, a KCNQ1 channel inhibitor, on insulin secretion in vitro and in vivo. By double-immunofluorescence staining, KCNQ1 was detected in insulin-positive b-cells and GLP-1-positive L-cells. Administration of chromanol 293B enhanced GSIS in cultured islets and intact animals. Along with the potentiated insulin secretion during oral glucose tolerance tests (OGTT), plasma GLP-1 level after gastric glucose load was increased in 293B treated mice. These data not only provided new evidence for the participation of KCNQ1 in GSIS at the level of pancreatic islet and intact animal but also indicated the potential linking role of GLP-1 between KCNQ1 and insulin secretion.

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“…Most Kv channels are expressed in excitable cells where, e.g., they regulate and modulate the resting potential and the threshold and duration of the action potential (1). The KCNQ1 channel (also called Kv7.1 or KvLQT1) differs from most other Kv channels in that it has key physiological roles in both excitable cells, such as cardiomyocytes (2,3) and pancreatic β-cells (4,5), and in nonexcitable cells, such as in epithelia (3,6). The KCNQ1 channels display diverse biophysical properties in different cell types, a diversity thought to be mainly due to the KCNQ1 channel's association with five tissue-specific, single-transmembrane segment KCNE β-subunits (KCNE1-5) (7-13).…”

mentioning

confidence: 99%

KCNE3 acts by promoting voltage sensor activation in KCNQ1

Barro-Soria

Perez

Larsson

2015

Proc. Natl. Acad. Sci. U.S.A.

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KCNE β-subunits assemble with and modulate the properties of voltage-gated K + channels. In the colon, stomach, and kidney, KCNE3 coassembles with the α-subunit KCNQ1 to form K + channels important for K + and Cl − secretion that appear to be voltageindependent. How KCNE3 subunits turn voltage-gated KCNQ1 channels into apparent voltage-independent KCNQ1/KCNE3 channels is not completely understood. Different mechanisms have been proposed to explain the effect of KCNE3 on KCNQ1 channels. Here, we use voltage clamp fluorometry to determine how KCNE3 affects the voltage sensor S4 and the gate of KCNQ1. We find that S4 moves in KCNQ1/KCNE3 channels, and that inward S4 movement closes the channel gate. However, KCNE3 shifts the voltage dependence of S4 movement to extreme hyperpolarized potentials, such that in the physiological voltage range, the channel is constitutively conducting. By separating S4 movement and gate opening, either by a mutation or PIP 2 depletion, we show that KCNE3 directly affects the S4 movement in KCNQ1. Two negatively charged residues of KCNE3 (D54 and D55) are found essential for the effect of KCNE3 on KCNQ1 channels, mainly exerting their effects by an electrostatic interaction with R228 in S4. Our results suggest that KCNE3 primarily affects the voltage-sensing domain and only indirectly affects the gate.proteins with a variety of crucial physiological roles. Most Kv channels are expressed in excitable cells where, e.g., they regulate and modulate the resting potential and the threshold and duration of the action potential (1). The KCNQ1 channel (also called Kv7.1 or KvLQT1) differs from most other Kv channels in that it has key physiological roles in both excitable cells, such as cardiomyocytes (2, 3) and pancreatic β-cells (4, 5), and in nonexcitable cells, such as in epithelia (3, 6). The KCNQ1 channels display diverse biophysical properties in different cell types, a diversity thought to be mainly due to the KCNQ1 channel's association with five tissue-specific, single-transmembrane segment KCNE β-subunits (KCNE1-5) (7-13). KCNQ1 α-subunit expressed by itself forms a voltage-dependent K + channel that opens at negative voltages ( Fig. 1 A and D). However, coexpression of KCNQ1 with KCNE1 slows the kinetics of activation and shifts the voltage dependence of activation to positive voltages ( Fig. 1 B and D) (7, 8), thereby generating the slowly activating, voltage-dependent I Ks current that controls the repolarization phase of cardiac action potentials. In contrast, coexpression of KCNQ1 with KCNE3 results in a constitutively conducting channel in the physiological voltage range of -80 to +40 mV ( Fig. 1 C and D), which is important for transport of water and salt in epithelial tissues, including those of the colon, small intestine, and airways (9,14,15). In addition, mutations of KCNE3 have been associated with cardiac arrhythmia (16,17) and diseases in the inner ear, such as Meniere's disease and tinnitus (18,19). Because KCNQ1/KCNE3 channels are necessary for water and salt secretion...

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The KCNQ1 Potassium Channel: From Gene to Physiological Function

Cited by 238 publications

References 106 publications

Identification and Functional Characterization of Ion Channels in CD34+ Hematopoietic Stem Cells from Human Peripheral Blood

Identification and Functional Characterization of Ion Channels in CD34+ Hematopoietic Stem Cells from Human Peripheral Blood

Chromanol 293B, an inhibitor of KCNQ1 channels, enhances glucose-stimulated insulin secretion and increases glucagon-like peptide-1 level in mice

KCNE3 acts by promoting voltage sensor activation in KCNQ1

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