G Protein-Gated Inwardly Rectifying Potassium Channel Subunits 1 and 2 are Down-Regulated in Rat Dorsal Root Ganglion Neurons and Spinal Cord after Peripheral Axotomy

• Published in: Molecular pain Vol. 11; p. 44
• Main Authors: Lyu, Chuang, Mulder, Jan, Barde, Swapnali, Sahlholm, Kristoffer, Zeberg, Hugo, Nilsson, Johanna, Århem, Peter, Hökfelt, Tomas, Fried, Kaj, Shi, Tie-Jun Sten
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 22.07.2015; Sage Publications Ltd; BioMed Central
• Subjects: Animals; Anterograde transport; Axonal Transport; Axotomy; Biomarkers - metabolism; Calbindin-D28K; Calcitonin; Calcitonin gene-related peptide; Calcium channels; Calcium-Binding Proteins - metabolism; Calretinin; Chronic pain; Dorsal horn; Dorsal root ganglia; Down-Regulation; Excitability; G Protein-Coupled Inwardly-Rectifying Potassium Channels - genetics; G Protein-Coupled Inwardly-Rectifying Potassium Channels - metabolism; Galanin - metabolism; Ganglia, Spinal - metabolism; Immunoreactivity; Localization; Lumbar Vertebrae - metabolism; Male; Medicin och hälsovetenskap; mRNA; Neurons; Neurons - metabolism; Nitric Oxide Synthase Type I - metabolism; Pain perception; Parvalbumin; Peripheral neuropathy; Potassium; Potassium channels; Potassium channels (inwardly-rectifying); Protein Subunits - metabolism; Proteins; Rats; Rats, Sprague-Dawley; Receptors, Somatostatin - metabolism; Retrograde transport; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sodium channels; Spinal cord; Spinal Cord - metabolism; Spinal Cord Dorsal Horn - metabolism; Spinal cord injuries; Vesicular Glutamate Transport Protein 1 - metabolism; Ca2+-binding proteins; GIRK channel; Nociceptor; Galanin; NPY; Nerve injury; Neuropeptides; Somatostatin; Axonal transport; CGRP; Neuropathic pain
• ISSN: 1744-8069; 1744-8069
• DOI: 10.1186/s12990-015-0044-z

Background Increased nociceptive neuronal excitability underlies chronic pain conditions. Various ion channels, including sodium, calcium and potassium channels have pivotal roles in the control of neuronal excitability. The members of the family of G protein-gated inwardly rectifying potassium (GIRK) channels, GIRK1–4, have been implicated in modulating excitability. Here, we investigated the expression and distribution of GIRK1 and GIRK2 in normal and injured dorsal root ganglia (DRGs) and spinal cord of rats. Results We found that ~70% of the DRG neurons expressed GIRK1, while only <10% expressed GIRK2. The neurochemical profiles of GIRK1- and GIRK2-immunoreactive neurons were characterized using the neuronal markers calcitonin gene-related peptide, isolectin-B4 and neurofilament-200, and the calcium-binding proteins calbindin D28k, calretinin, parvalbumin and secretagogin. Both GIRK subunits were expressed in DRG neurons with nociceptive characteristics. However, while GIRK1 was widely expressed in several sensory neuronal subtypes, GIRK2 was detected mainly in a group of small C-fiber neurons. In the spinal dorsal horn, GIRK1- and −2-positive cell bodies and processes were mainly observed in lamina II, but also in superficial and deeper layers. Abundant GIRK1-, but not GIRK2-like immunoreactivity, was found in the ventral horn (laminae VI–X). Fourteen days after axotomy, GIRK1 and GIRK2 were down-regulated in DRG neurons at the mRNA and protein levels. Both after axotomy and rhizotomy there was a reduction of GIRK1- and −2-positive processes in the dorsal horn, suggesting a presynaptic localization of these potassium channels. Furthermore, nerve ligation caused accumulation of both subunits on both sides of the lesion, providing evidence for anterograde and retrograde fast axonal transport. Conclusions Our data support the hypothesis that reduced GIRK function is associated with increased neuronal excitability and causes sensory disturbances in post-injury conditions, including neuropathic pain.