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G Protein-Gated Inwardly Rectifying Potassium Channel Subunit 3 is Upregulated in Rat DRGs and Spinal Cord After Peripheral Nerve Injury

Authors Lyu C, Lyu GW, Mulder J, Martinez A, Shi TJS

Received 7 October 2019

Accepted for publication 28 January 2020

Published 17 February 2020 Volume 2020:13 Pages 419—429

DOI https://doi.org/10.2147/JPR.S233744

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr E Alfonso Romero-Sandoval


Chuang Lyu,1 Gong-Wei Lyu,2 Jan Mulder,3,4 Aurora Martinez,5 Tie-Jun Sten Shi5

1State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, People’s Republic of China; 2Department of Neurology, 1st Hospital of Harbin Medical University, Harbin 150001, People’s Republic of China; 3Department of Neuroscience, Karolinska Institutet, Stockholm SE-171 77, Sweden; 4Science for Life Laboratory, Karolinska Institutet, Stockholm SE-171 65, Sweden; 5Department of Biomedicine, University of Bergen, Bergen 5009, Norway

Correspondence: Chuang Lyu Tel +86 13304503501
Email htylv123@126.com
Tie-Jun Sten Shi Tel +47 45392855
Email tiejun.shi@uib.no

Background: G protein-gated inwardly rectifying potassium (GIRK) channels are involved in the regulation of neuronal excitability. Four GIRK subunits (GIRK1-4) are expressed in rat dorsal root ganglia (DRGs). Recently, we have characterized the expression of GIRK1 and − 2, and both are downregulated in rat DRGs and spinal cord after a complete sciatic nerve transection (axotomy). Here, we aimed to study the neurochemical characteristics of GIRK3, and its regulation in rat DRGs and spinal cord induced by nerve injury.
Methods: A sciatic nerve axotomy was performed to study the influences of injury on GIRK3 expression in DRGs and spinal cord. A dorsal root rhizotomy and a sciatic nerve crush were employed to study the axonal transport of GIRK3 protein, respectively. Immunohistochemistry analysis was employed for investigating the neurochemical characteristics of GIRK3.
Results: In control DRGs, ∼ 18% of neuron profiles (NPs) were GIRK3-positive (+), and ∼ 41%, ∼ 48% and ∼ 45% of GIRK3+ NPs were CGRP+, IB4+ and NF200+, respectively. GIRK3-like immunoreactivity was observed in glabrous skin of hind paws and axons originating from DRG neurons. Fourteen days after axotomy, more than one-third of DRG NPs were GIRK3+, and among these ∼ 51% and ∼ 56% coexpressed galanin and neuropeptide Y, respectively. In control animals, a small group of interneurons found in the dorsal horn was GIRK3+. In addition, GIRK3+ processes could be observed in superficial laminae of spinal dorsal horn. After nerve injury, the intensity of GIRK3-like immunoreactivity in the superficial layers was increased. Evidence based on rhizotomy and sciatic nerve crush indicated both anterograde and retrograde transport of GIRK3.
Conclusion: Our study demonstrates that GIRK3 is expressed in sensory neurons and spinal cord. GIRK3 has both anterograde and retrograde axonal transport. GIRK3 expression can be regulated by peripheral nerve injury.

Keywords: GIRK channels, Kir3, axotomy, DRGs, spinal cord, chronic pain

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