An intracellular TRP channel Mediates Ca2+ Release from a non-ER Ca2+ store in Dorsal Root Ganglion Neurons
Zhuan ZhouShujiang ShangTao LiuMeiqin HuLianghong ZhengLi WangQihui WuZuying ChaiRong HuangXiaoyu ZhangXi WuLei SunBin LiuHuadong XUSasa TengYeshi WangChen ZhangFukang ZhangXH FengDesheng ZhuChanghe WangMichale Xi Zhu
摘要：The transient receptor potential X（TRP-X） is a non-selective cation channel implicated in physiological relevance. Here we show that TRP-X elevates intracellular Ca2+ concentration（[Ca2+]i） in dorsal root ganglion（DRG） neurons not only in the presence but also in the absence of extracellular Ca2+. Pharmacological and immunocytochemical analyses revealed the presence of TRP-X on both the plasma membrane and in a nonER organelle（n ER）. Confocal line-scan imaging demonstrated a close association of Ca2+ signals elicited by TRP-X activation with individual n ER（"n ER Ca2+ spark"）. In physiological solutions, the TRP-X mediated lysosomal Ca2+ release contributed to 40% of the overall [Ca2+]i rise and directly triggered vesicle exocytosis and neuropeptide release. The n ER-localized TRP-X in DRG neurons also modulated TRP-X agonistinduced pain response and heat hyperalgesia in wild type but not TRP-X-deficient mice. Thus, in addition to working via Ca2+ influx, TRP-X triggers vesicle exocytosis in sensory neurons and modulates pain sensation by releasing Ca2+ from non-ER.