Shaker Family K<i>v</i>1 Voltage‐Gated Potassium Channels in Mammalian Brain Neurons

Vacher, Hélène; Trimmer, James S.

doi:10.1002/9780470429907.ch5

Cited by 2 publications

(3 citation statements)

References 152 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Heteromeric assembly of different subunits yields channels with intermediate trafficking characteristics (194). Thus, the subunit composition of K v 1 channels not only determines their gating and kinetic properties, but also dramatically affects their expression and localization (340). …”

Section: Voltage-dependent Potassium Channel Localization In Mammmentioning

confidence: 99%

“…Moreover, heteromeric assembly with one another, and co-assembly with auxiliary K v β subunits can generate a diversity of function from the resultant α 4 β 4 channel complexes (340). In neurons K v 1 channels are found predominantly on axons and nerve terminals, although dendritic expression is also found in certain neurons (335).…”

Section: Voltage-dependent Potassium Channel Localization In Mammmentioning

confidence: 99%

See 1 more Smart Citation

Localization and Targeting of Voltage-Dependent Ion Channels in Mammalian Central Neurons

Vacher

Mohapatra²,

Trimmer

2008

Physiological Reviews

Self Cite

442

469

View full text Add to dashboard Cite

The intrinsic electrical properties and the synaptic input-output relationships of neurons are governed by the action of voltage-dependent ion channels. The localization of specific population of ion channels with distinct functional properties at discrete sites in neurons dramatically impacts excitability and synaptic transmission. Molecular cloning studies have revealed a large family of genes encoding voltage-dependent ion channel principal and auxiliary subunits, most of which are expressed in mammalian central neurons. Much recent effort has focused on determining which of these subunits co-assemble into native neuronal channel complexes, and the cellular and subcellular distributions of these complexes, as a crucial step in understanding the contribution of these channels to specific aspects of neuronal function. Here we review progress made on recent studies aimed at determining the cellular and subcellular distribution of specific ion channel subunits in mammalian brain neurons using in situ hybridization, and immunohistochemistry. We also discuss the repertoire of ion channel subunits in specific neuronal compartments and implications for neuronal physiology. Finally, we discuss the emerging mechanisms for determining the discrete subcellular distributions observed for many neuronal ion channels. I. OVERVIEW OF MAMMALIAN BRAIN VOLTAGE-DEPENDENT ION CHANNELS A. IntroductionMammalian central neurons express a large repertoire of voltage-dependent ion channels (VDICs) that form selective pores in the neuronal membrane and confer diverse properties of intrinsic neuronal excitability. This allows mammalian neurons to display a richness of firing behaviors over a wide range of stimuli and firing frequencies. The complex electrical behavior of mammalian neurons is due to a huge array of VDICs with distinct ion flux rates and selectivity, although the major VDICs underlying neuronal excitability and electrical signaling are those selective for Na + , K + and Ca 2+ ions. Neuronal VDICs also exhibit widely differing properties of how sensitive their gating, or the opening or closing of the channels pore, is to changes in membrane potential. Different VDICs also differ in the kinetics of these gating events. Importantly in the terms of mammalian brain, different VDICs differ widely in their cellular expression and subcellular localization, impacting their relative contribution to brain

show abstract

Section: Voltage-dependent Potassium Channel Localization In Mammmentioning

confidence: 99%

Section: Voltage-dependent Potassium Channel Localization In Mammmentioning

confidence: 99%

Localization and Targeting of Voltage-Dependent Ion Channels in Mammalian Central Neurons

Vacher

Mohapatra²,

Trimmer

2008

Physiological Reviews

Self Cite

442

469

View full text Add to dashboard Cite

show abstract

“…5 min infusion, 10 min post-end of infusion C plasma 7.7 μM, brain exposure 25 μM; n = 3). Due to the multiple potassium ion channels expressed in the brain, differential distribution in species, and the difficulty in screening compounds broadly for ion channel activity, we focused our efforts on significantly reducing brain penetration while maintaining good efficacy in the rabbit PD model. Our efforts to identify and further optimize this series to our current clinical candidate will be disclosed in a subsequent manuscript.…”

mentioning

confidence: 99%

Discovery of 5-Phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine as a PotentI_KurInhibitor

Finlay

Johnson

Lloyd

et al. 2016

ACS Med. Chem. Lett.

View full text Add to dashboard Cite

A new series of phenylquinazoline inhibitors of K v 1.5 is disclosed. The series was optimized for K v 1.5 potency, selectivity versus hERG, pharmacokinetic exposure, and pharmacodynamic potency. 5-Phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)-quinazolin-4-amine (13k) was identified as a potent and ion channel selective inhibitor with robust efficacy in the preclinical rat ventricular effective refractory period (VERP) model and the rabbit atrial effective refractory period (AERP) model.

show abstract

Shaker Family Kv1 Voltage‐Gated Potassium Channels in Mammalian Brain Neurons

Cited by 2 publications

References 152 publications

Localization and Targeting of Voltage-Dependent Ion Channels in Mammalian Central Neurons

Localization and Targeting of Voltage-Dependent Ion Channels in Mammalian Central Neurons

Discovery of 5-Phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine as a PotentI_KurInhibitor

Contact Info

Product

Resources

About

Shaker Family Kv1 Voltage‐Gated Potassium Channels in Mammalian Brain Neurons

Cited by 2 publications

References 152 publications

Localization and Targeting of Voltage-Dependent Ion Channels in Mammalian Central Neurons

Localization and Targeting of Voltage-Dependent Ion Channels in Mammalian Central Neurons

Discovery of 5-Phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine as a PotentIKurInhibitor

Contact Info

Product

Resources

About

Discovery of 5-Phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine as a PotentI_KurInhibitor