BK Potassium Channels Suppress Cavα2δ Subunit Function to Reduce Inflammatory and Neuropathic Pain

Cell Reports
Fang-Xiong ZhangGerald W Zamponi

Abstract

Cavα2δ subunits contribute to the cell-surface expression of Cav2 calcium channels. Upregulation of Cavα2δ-1 in dorsal root ganglion neurons occurs after nerve injury and results in an increased synaptic abundance of Cav2.2 channels in the spinal dorsal horn, thus enhancing the transmission of pain signals. Here, we report that large conductance calcium-activated potassium (BK) channels interact with the Cavα2δ subunit. Coexpression of BK channels with the Cav2 calcium channels reduces their cell-surface expression and whole-cell current density by competing the Cavα2δ subunit away from the Cav2 complex. Biochemical analysis reveals that the extracellular N terminus region of the BK channel is the key molecular determinant of this effect. Intrathecally delivered virus constructs encoding a membrane-anchored BK channel N terminus peptide produces long-lasting analgesia in mouse models of inflammatory and neuropathic pain. Collectively, our data reveal an endogenous ligand of the Cavα2δ subunit with analgesic properties.

Citations

Nov 16, 2019·Pain Management·Seung Woo Baek, Michael A Erdek
Apr 4, 2020·The Journal of General Physiology·Xueyong WangMark M Rich
Sep 11, 2019·Nature Neuroscience·Junting HuangGerald W Zamponi
May 1, 2020·Frontiers in Cellular Neuroscience·Sascha R A AllesTerrance P Snutch
Oct 27, 2018·Neuronal Signaling·Lindsey A Chew, Rajesh Khanna
Dec 13, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jörg Striessnig
Jul 2, 2020·Pflügers Archiv : European journal of physiology·Cornelia AblingerGerald J Obermair
Oct 24, 2020·Frontiers in Cellular Neuroscience·Peter A Smith
Feb 13, 2021·The FEBS Journal·Maria A Gandini, Gerald W Zamponi
Jun 11, 2020·Current Opinion in Neurobiology·William Christopher Risher, Cagla Eroglu
Nov 17, 2021·The Journal of Physiology·Kathleen A BeesonEric Schnell

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