{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:13:18Z","timestamp":1790255598266,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2014,6,19]],"date-time":"2014-06-19T00:00:00Z","timestamp":1403136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH\/NINDS","award":["R21 NS077330-01A1"],"award-info":[{"award-number":["R21 NS077330-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2014,8,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>A previous study indicates that store\u2010operated calcium channels (SOCs) play a role in pain hypersensitivity. Here we report for the first time that SOCs are expressed and functional in spinal cord dorsal horn neurons.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Using the small inhibitory RNA knockdown approach, we have demonstrated that Orai1 is necessary, and both STIM1 and STIM2 are important for SOC entry and SOC current in dorsal horn neurons.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Our findings demonstrate that STIM1, STIM2 and Orai1 play an important role in resting Ca<jats:sup>2+<\/jats:sup>homeostasis.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Our results also indicate that SOCs are involved in the function of neurokinin 1 receptors and activation of SOCs produces an excitatory action in dorsal horn neurons.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>The present study reveals that a novel calcium signal mediated by SOCs is present in dorsal horn neurons and provides a potential mechanism for SOC inhibition\u2010induced central analgesia.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Store\u2010operated calcium channels (SOCs) are calcium\u2010selective cation channels that mediate calcium entry in many different cell types. Store\u2010operated calcium entry (SOCE) is involved in various cellular functions. Increasing evidence suggests that impairment of SOCE is responsible for numerous disorders. A previous study demonstrated that YM\u201058483, a potent SOC inhibitor, strongly attenuates chronic pain by systemic or intrathecal injection and completely blocks the second phase of formalin\u2010induced spontaneous nocifensive behaviour, suggesting a potential role of SOCs in central sensitization. However, the expression of SOCs, their molecular identity and function in spinal cord dorsal horn neurons remain elusive. Here, we demonstrate that SOCs are expressed in dorsal horn neurons. Depletion of calcium stores from the endoplasmic reticulum (ER) induced large sustained calcium entry, which was blocked by SOC inhibitors, but not by voltage\u2010gated calcium channel blockers. Depletion of ER calcium stores activated inward calcium\u2010selective currents, which was reduced by replacing Ca<jats:sup>2+<\/jats:sup>with Ba<jats:sup>2+<\/jats:sup>and reversed by SOC inhibitors. Using the small inhibitory RNA knockdown approach, we identified both STIM1 and STIM2 as important mediators of SOCE and SOC current, and Orai1 as a key component of the Ca<jats:sup>2+<\/jats:sup>release\u2010activated Ca<jats:sup>2+<\/jats:sup>channels in dorsal horn neurons. Knockdown of STIM1, STIM2 or Orai1 decreased resting Ca<jats:sup>2+<\/jats:sup>levels. We also found that activation of neurokinin 1 receptors led to SOCE and activation of SOCs produced an excitatory action in dorsal horn neurons. Our findings reveal that a novel SOC signal is present in dorsal horn neurons and may play an important role in pain transmission.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2014.275065","type":"journal-article","created":{"date-parts":[[2014,5,24]],"date-time":"2014-05-24T04:19:41Z","timestamp":1400905181000},"page":"3443-3461","source":"Crossref","is-referenced-by-count":43,"title":["Native store\u2010operated calcium channels are functionally expressed in mouse spinal cord dorsal horn neurons and regulate resting calcium homeostasis"],"prefix":"10.1113","volume":"592","author":[{"given":"Jingsheng","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology Drexel University College of Medicine Philadelphia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology Drexel University College of Medicine Philadelphia 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