A-Type KV Channels in Dorsal Root Ganglion Neurons: Diversity, Function, and Dysfunction

A-type voltage-gated potassium (Kv) channels are major regulators of neuronal excitability that have been mainly characterized in the central nervous system. By contrast, there is a paucity of knowledge about the molecular physiology of these Kv channels in the peripheral nervous system, including h...

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Main Authors: Benjamin M. Zemel, David M. Ritter, Manuel Covarrubias, Tanziyah Muqeem
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-08-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnmol.2018.00253/full
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spelling doaj-9464f23bce964aa3903bd2e228adf2302020-11-24T23:40:06ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-08-011110.3389/fnmol.2018.00253388817A-Type KV Channels in Dorsal Root Ganglion Neurons: Diversity, Function, and DysfunctionBenjamin M. Zemel0David M. Ritter1Manuel Covarrubias2Tanziyah Muqeem3Vollum Institute, Oregon Health and Science University, Portland, OR, United StatesDivision of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Neuroscience, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College and Jefferson College of Life Sciences at Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Neuroscience, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College and Jefferson College of Life Sciences at Thomas Jefferson University, Philadelphia, PA, United StatesA-type voltage-gated potassium (Kv) channels are major regulators of neuronal excitability that have been mainly characterized in the central nervous system. By contrast, there is a paucity of knowledge about the molecular physiology of these Kv channels in the peripheral nervous system, including highly specialized and heterogenous dorsal root ganglion (DRG) neurons. Although all A-type Kv channels display pore-forming subunits with similar structural properties and fast inactivation, their voltage-, and time-dependent properties and modulation are significantly different. These differences ultimately determine distinct physiological roles of diverse A-type Kv channels, and how their dysfunction might contribute to neurological disorders. The importance of A-type Kv channels in DRG neurons is highlighted by recent studies that have linked their dysfunction to persistent pain sensitization. Here, we review the molecular neurophysiology of A-type Kv channels with an emphasis on those that have been identified and investigated in DRG nociceptors (Kv1.4, Kv3.4, and Kv4s). Also, we discuss evidence implicating these Kv channels in neuropathic pain resulting from injury, and present a perspective of outstanding challenges that must be tackled in order to discover novel treatments for intractable pain disorders.https://www.frontiersin.org/article/10.3389/fnmol.2018.00253/fullKv channelA-typedorsal root ganglionpainKv1.4Kv3.4
collection DOAJ
language English
format Article
sources DOAJ
author Benjamin M. Zemel
David M. Ritter
Manuel Covarrubias
Tanziyah Muqeem
spellingShingle Benjamin M. Zemel
David M. Ritter
Manuel Covarrubias
Tanziyah Muqeem
A-Type KV Channels in Dorsal Root Ganglion Neurons: Diversity, Function, and Dysfunction
Frontiers in Molecular Neuroscience
Kv channel
A-type
dorsal root ganglion
pain
Kv1.4
Kv3.4
author_facet Benjamin M. Zemel
David M. Ritter
Manuel Covarrubias
Tanziyah Muqeem
author_sort Benjamin M. Zemel
title A-Type KV Channels in Dorsal Root Ganglion Neurons: Diversity, Function, and Dysfunction
title_short A-Type KV Channels in Dorsal Root Ganglion Neurons: Diversity, Function, and Dysfunction
title_full A-Type KV Channels in Dorsal Root Ganglion Neurons: Diversity, Function, and Dysfunction
title_fullStr A-Type KV Channels in Dorsal Root Ganglion Neurons: Diversity, Function, and Dysfunction
title_full_unstemmed A-Type KV Channels in Dorsal Root Ganglion Neurons: Diversity, Function, and Dysfunction
title_sort a-type kv channels in dorsal root ganglion neurons: diversity, function, and dysfunction
publisher Frontiers Media S.A.
series Frontiers in Molecular Neuroscience
issn 1662-5099
publishDate 2018-08-01
description A-type voltage-gated potassium (Kv) channels are major regulators of neuronal excitability that have been mainly characterized in the central nervous system. By contrast, there is a paucity of knowledge about the molecular physiology of these Kv channels in the peripheral nervous system, including highly specialized and heterogenous dorsal root ganglion (DRG) neurons. Although all A-type Kv channels display pore-forming subunits with similar structural properties and fast inactivation, their voltage-, and time-dependent properties and modulation are significantly different. These differences ultimately determine distinct physiological roles of diverse A-type Kv channels, and how their dysfunction might contribute to neurological disorders. The importance of A-type Kv channels in DRG neurons is highlighted by recent studies that have linked their dysfunction to persistent pain sensitization. Here, we review the molecular neurophysiology of A-type Kv channels with an emphasis on those that have been identified and investigated in DRG nociceptors (Kv1.4, Kv3.4, and Kv4s). Also, we discuss evidence implicating these Kv channels in neuropathic pain resulting from injury, and present a perspective of outstanding challenges that must be tackled in order to discover novel treatments for intractable pain disorders.
topic Kv channel
A-type
dorsal root ganglion
pain
Kv1.4
Kv3.4
url https://www.frontiersin.org/article/10.3389/fnmol.2018.00253/full
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AT manuelcovarrubias atypekvchannelsindorsalrootganglionneuronsdiversityfunctionanddysfunction
AT tanziyahmuqeem atypekvchannelsindorsalrootganglionneuronsdiversityfunctionanddysfunction
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