Journal of Pain Research (Feb 2020)
G Protein-Gated Inwardly Rectifying Potassium Channel Subunit 3 is Upregulated in Rat DRGs and Spinal Cord After Peripheral Nerve Injury
Abstract
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, NorwayCorrespondence: Chuang Lyu Tel +86 13304503501Email [email protected] Sten Shi Tel +47 45392855Email [email protected]: 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
