期刊
JOURNAL OF NEUROSCIENCE
卷 25, 期 21, 页码 5109-5116出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0237-05.2005
关键词
TRPV1; VR1; nociception; strength; pain
Transient receptor potential (TRP) channels detect diverse sensory stimuli, including alterations in osmolarity. However, a molecular detector of noxious hypertonic stimuli has not yet been identified. We show here that acute pain-related behavior evoked by elevated ionic strength is abolished in TRP vanilloid subtype 1 ( TRPV1)-null mice and inhibited by iodoresiniferatoxin, a potent TRPV1 antagonist. Electrophysiological recordings demonstrate a novel form of ion channel modulation by which extracellular Na+, Mg2+, and Ca2+ ions sensitize and activate the capsaicin receptor, TRPV1. At room temperature, increasing extracellular Mg2+ ( from 1 to 5mM) or Na+ (+50 mM) increased ligand-activated currents up to fourfold, and 10mM Mg2+ reduced the EC50 for activation by capsaicin from 890 to 450 nM. Moreover, concentrations of divalent cations >10mM directly gate the receptor. These effects occur via electrostatic interactions with two glutamates (E600 and E648) formerly identified as proton-binding residues. Furthermore, phospholipase C-mediated signaling enhances the effects of cations, and physiological concentrations of cations contribute to the bradykinin-evoked activation of TRPV1 and the sensitization of the receptor to heat. Thus, the modulation of TRPV1 by cationic strength may contribute to inflammatory pain signaling.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据