Tyrosine phosphorylation of Kir3.1 in spinal cord is induced by acute inflammation, chronic neuropathic pain, and behavioral stress

Danielle L. Ippolito, Mei Xu, Michael R. Bruchas, Kevin Wickman, Charles Chavkin

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Tyrosine phosphorylation is an important means of regulating ion channel function. Our previous gene expression studies using the Xenopus laevis oocyte system suggested that tyrosine phosphorylation of G-protein-gated inwardly rectifying potassium channels (Kir3 or GIRK) suppressed basal channel conductance and accelerated channel deactivation. To assess whether similar mechanisms regulate Kir3 function in mammalian cells, we developed and characterized a phosphoselective antibody recognizing Kir3.1 phosphorylated at tyrosine 12 in the N-terminal domain and then probed for evidence of Kir3.1 phosphorylation in cultured mammalian cell and spinal cord. The antibody was found to discriminate between the phospho-Tyr 12 of Kir3.1 and the native state in transfected cell lines and in primary cultures of mouse atria. Following either mouse hindpaw formalin injection or sciatic nerve ligation, pY12-Kir3.1 immunoreactivity was enhanced unilaterally in the superficial layers of the spinal cord dorsal horn, regions previously described as expressing K ir3.1 channels. Mice lacking Kir3.1 following targeted gene disruption did not show specific pY12-Kir3.1 immunoreactivity after sciatic nerve ligation. Further, mice exposed to repeatedly forced swim stress showed bilateral enhancement in pY12-Kir3.1 in the dorsal horn. This study provides evidence that Kir3 tyrosine phosphorylation occurred during acute and chronic inflammatory pain and under behavioral stress. The reduction in Kir3 channel activity is predicted to enhance neuronal excitability under physiologically relevant conditions and may mediate a component of the adaptive physiological response.

Original languageEnglish (US)
Pages (from-to)41683-41693
Number of pages11
JournalJournal of Biological Chemistry
Volume280
Issue number50
DOIs
StatePublished - Dec 16 2005

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