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J Exp Neurosci. 2017 Sep 14;11:1179069517726996. doi: 10.1177/1179069517726996. eCollection 2017.

Slick (Kcnt2) Sodium-Activated Potassium Channels Limit Peptidergic Nociceptor Excitability and Hyperalgesia.

Author information

1
Neuroscience Program, The State University of New York - University at Buffalo, Buffalo, NY, USA.
2
Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, The State University of New York - University at Buffalo, Buffalo, NY, USA.
3
Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, The State University of New York - University at Buffalo, Buffalo, NY, USA.

Abstract

The Slick (Kcnt2) sodium-activated potassium (KNa) channel is a rapidly gating and weakly voltage-dependent and sodium-dependent potassium channel with no clearly defined physiological function. Within the dorsal root ganglia (DRGs), we show Slick channels are exclusively expressed in small-sized and medium-sized calcitonin gene-related peptide (CGRP)-containing DRG neurons, and a pool of channels are localized to large dense-core vesicles (LDCV)-containing CGRP. We stimulated DRG neurons for CGRP release and found Slick channels contained within CGRP-positive LDCV translocated to the neuronal membrane. Behavioral studies in Slick knockout (KO) mice indicated increased basal heat detection and exacerbated thermal hyperalgesia compared with wild-type littermate controls during neuropathic and chronic inflammatory pain. Electrophysiologic recordings of DRG neurons from Slick KO mice revealed that Slick channels contribute to outward current, propensity to fire action potentials (APs), and to AP properties. Our data suggest that Slick channels restrain the excitability of CGRP-containing neurons, diminishing pain behavior after inflammation and injury.

KEYWORDS:

CGRP; DRG neurons; Ion channels; chronic pain; thermal nociception

Conflict of interest statement

Declaration of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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