The voltage-gated potassium channel Kv7.1 and its auxiliary subunit KCNE1 are expressed in the heart and give rise to the major repolarization current. The interaction of Kv7.1 with the single transmembrane helix of KCNE1 considerably slows channel activation and deactivation, raises single-channel conductance, and prevents slow voltage-dependent inactivation. We built a Kv7.1-KCNE1 model-structure. The model-structure agrees with previous disulfide mapping studies and enables us to derive molecular interpretations of electrophysiological recordings that we obtained for two KCNE1 mutations. An elastic network analysis of Kv7.1 fluctuations in the presence and absence of KCNE1 suggests a mechanistic perspective on the known effects of KCNE1 on Kv7.1 function: slow deactivation is attributed to the low mobility of the voltage-sensor domains upon KCNE1 binding, abolishment of voltage-dependent inactivation could result from decreased fluctuations in the external vestibule, and amalgamation of the fluctuations in the pore region is associated with enhanced ion conductivity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.str.2012.05.016 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The potassium channel subunit K1.8 () is essential for the distinctive outwardly rectifying conductances of type I and II vestibular hair cells.
Elife
December 2024
Department of Neurobiology, University of Chicago, Chicago, United States.
In amniotes, head motions and tilt are detected by two types of vestibular hair cells (HCs) with strikingly different morphology and physiology. Mature type I HCs express a large and very unusual potassium conductance, g, which activates negative to resting potential, confers very negative resting potentials and low input resistances, and enhances an unusual non-quantal transmission from type I cells onto their calyceal afferent terminals. Following clues pointing to K1.
View Article and Find Full Text PDFIntegrated responses of the SIP syncytium generate a major motility pattern in the colon.
J Physiol
December 2024
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA.
The peristaltic reflex has been a central concept in gastrointestinal motility; however, evidence was published recently suggesting that post-stimulus responses that follow inhibitory neural responses provide the main propulsive force in colonic motility. This new concept was based on experiments on proximal colon where enteric inhibitory neural inputs are mainly nitrergic. However, the nature of inhibitory neural inputs changes from proximal to distal colon where purinergic inhibitory regulation dominates.
View Article and Find Full Text PDFA Rich Conformational Palette Underlies Human Ca2.1-Channel Availability.
bioRxiv
September 2024
Division of Cell and Neurobiology, Department of Biomedical and Clinical Sciences, Linköping University; SE-581 85 Linköping, Sweden.
Depolarization-evoked opening of Ca2.1 (P/Q-type) Ca-channels triggers neurotransmitter release, while voltage-dependent inactivation (VDI) limits channel availability to open, contributing to synaptic plasticity. The mechanism of Ca2.
View Article and Find Full Text PDFA novel gene variant in the voltage-dependent Kv3.3 channel in an atypical form of SCA13 with dominant central vertigo.
Front Cell Neurosci
October 2024
Institute for Physiology and Pathophysiology and Center for Mind Brain and Behavior (CMBB), Philipps-University Marburg, Marburg, Germany.
Potassium channel mutations play an important role in neurological diseases, such as spinocerebellar ataxia (SCA). SCA is a heterogeneous autosomal-dominant neurodegenerative disorder with multiple sub-entities, such as SCA13, which is characterized by mutations in the voltage-gated potassium channel Kv3.3 ().
View Article and Find Full Text PDFInactivation induced by pathogenic Ca1.3 L-type Ca-channel variants enhances sensitivity for dihydropyridine Ca channel blockers.
Br J Pharmacol
January 2025
Department of Pharmacology and Toxicology, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria.
Background And Purpose: Pathogenic gain-of-function mutations in Ca1.3 L-type voltage-gated Ca-channels (CACNA1D) cause neurodevelopmental disorders with or without endocrine symptoms. We aimed to confirm a pathogenic gain-of function phenotype of CACNA1D de novo missense mutations A749T and L271H, and investigated the molecular mechanism causing their enhanced sensitivity for the Ca-channel blocker isradipine, a potential therapeutic for affected patients.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!