scholarly journals EAG channels expressed in microvillar photoreceptors are unsuited to diurnal vision

2017 ◽  
Vol 595 (16) ◽  
pp. 5465-5479 ◽  
Author(s):  
Esa-Ville Immonen ◽  
Andrew S. French ◽  
Päivi H. Torkkeli ◽  
Hongxia Liu ◽  
Mikko Vähäsöyrinki ◽  
...  
Keyword(s):  
Eag Channels

Molecular Determinants of Inactivation and Dofetilide Block inether a-go-go (EAG) Channels and EAG-Related K+ Channels

2001 ◽  
Vol 60 (6) ◽  
pp. 1343-1348 ◽  
Author(s):  
Eckhard Ficker ◽  
Wolfgang Jarolimek ◽  
Arthur M. Brown
Keyword(s):  
K Channels ◽  
Molecular Determinants ◽  
Eag Channels

scholarly journals Discovery of a heme-binding domain in a neuronal voltage-gated potassium channel

2020 ◽  
Vol 295 (38) ◽  
pp. 13277-13286
Author(s):  
Mark J. Burton ◽  
Joel Cresser-Brown ◽  
Morgan Thomas ◽  
Nicola Portolano ◽  
Jaswir Basran ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Normal Function ◽  
Pas Domain ◽  
Heme Binding ◽  
Channel Activity ◽  
Action Potential Firing ◽  
Voltage Gated ◽  
Conserved Domain ◽  
Potential Firing ◽  
Eag Channels

The EAG (ether-à-go-go) family of voltage-gated K+ channels are important regulators of neuronal and cardiac action potential firing (excitability) and have major roles in human diseases such as epilepsy, schizophrenia, cancer, and sudden cardiac death. A defining feature of EAG (Kv10–12) channels is a highly conserved domain on the N terminus, known as the eag domain, consisting of a Per–ARNT–Sim (PAS) domain capped by a short sequence containing an amphipathic helix (Cap domain). The PAS and Cap domains are both vital for the normal function of EAG channels. Using heme-affinity pulldown assays and proteomics of lysates from primary cortical neurons, we identified that an EAG channel, hERG3 (Kv11.3), binds to heme. In whole-cell electrophysiology experiments, we identified that heme inhibits hERG3 channel activity. In addition, we expressed the Cap and PAS domain of hERG3 in Escherichia coli and, using spectroscopy and kinetics, identified the PAS domain as the location for heme binding. The results identify heme as a regulator of hERG3 channel activity. These observations are discussed in the context of the emerging role for heme as a regulator of ion channel activity in cells.

scholarly journals Voltage-dependent activation in EAG channels follows a ligand-receptor rather than a mechanical-lever mechanism

2019 ◽  
Vol 294 (16) ◽  
pp. 6506-6521 ◽  
Author(s):  
Olfat A. Malak ◽  
Grigory S. Gluhov ◽  
Anastasia V. Grizel ◽  
Kseniya S. Kudryashova ◽  
Olga S. Sokolova ◽  
...  
Keyword(s):  
Voltage Dependent ◽  
Lever Mechanism ◽  
Eag Channels

scholarly journals Chlorpromazine binding to the PAS domains uncovers the effect of ligand modulation on EAG channel activity

2020 ◽  
Vol 295 (13) ◽  
pp. 4114-4123 ◽  
Author(s):  
Ze-Jun Wang ◽  
Stephanie M. Soohoo ◽  
Purushottam B. Tiwari ◽  
Grzegorz Piszczek ◽  
Tinatin I. Brelidze
Keyword(s):  
Ligand Binding ◽  
Cancer Progression ◽  
Neurological Disorders ◽  
Neuronal Excitability ◽  
Tryptophan Fluorescence ◽  
Structural Similarity ◽  
Pas Domain ◽  
Channel Activity ◽  
Binding Domains ◽  
Eag Channels

Ether-a-go-go (EAG) potassium selective channels are major regulators of neuronal excitability and cancer progression. EAG channels contain a Per–Arnt–Sim (PAS) domain in their intracellular N-terminal region. The PAS domain is structurally similar to the PAS domains in non-ion channel proteins, where these domains frequently function as ligand-binding domains. Despite the structural similarity, it is not known whether the PAS domain can regulate EAG channel function via ligand binding. Here, using surface plasmon resonance, tryptophan fluorescence, and analysis of EAG currents recorded in Xenopus laevis oocytes, we show that a small molecule chlorpromazine (CH), widely used as an antipsychotic medication, binds to the isolated PAS domain of EAG channels and inhibits currents from these channels. Mutant EAG channels that lack the PAS domain show significantly lower inhibition by CH, suggesting that CH affects currents from EAG channels directly through the binding to the PAS domain. Our study lends support to the hypothesis that there are previously unaccounted steps in EAG channel gating that could be activated by ligand binding to the PAS domain. This has broad implications for understanding gating mechanisms of EAG and related ERG and ELK K+ channels and places the PAS domain as a new target for drug discovery in EAG and related channels. Up-regulation of EAG channel activity is linked to cancer and neurological disorders. Our study raises the possibility of repurposing the antipsychotic drug chlorpromazine for treatment of neurological disorders and cancer.

scholarly journals Cytoplasmic Domains of EAG Channels

2012 ◽  
Vol 102 (3) ◽  
pp. 212a
Author(s):  
Joao Morais-Cabral
Keyword(s):  
Cytoplasmic Domains ◽  
Eag Channels

scholarly journals EAG Channel PAS Domain Binder Inhibits Currents from EAG Channels and Decreases Tumor Growth in Zebrafish Xenograft Model

2020 ◽  
Vol 118 (3) ◽  
pp. 268a
Author(s):  
Ze-Jun Wang ◽  
Pareesa Kamgar-Dayhoff ◽  
Purushottam B. Tiwari ◽  
Eric Glasgow ◽  
Tinatin I. Brelidze
Keyword(s):  
Tumor Growth ◽  
Xenograft Model ◽  
Pas Domain ◽  
Eag Channels

scholarly journals Human EAG channels are directly modulated by PIP2 as revealed by electrophysiological and optical interference investigations

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Bo Han ◽  
Kunyan He ◽  
Chunlin Cai ◽  
Yin Tang ◽  
Linli Yang ◽  
...  
Keyword(s):  
Optical Interference ◽  
Eag Channels
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