{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:15:07Z","timestamp":1791252907983,"version":"4.1.0"},"reference-count":28,"publisher":"Society for Neuroscience","issue":"3","license":[{"start":{"date-parts":[[2004,7,21]],"date-time":"2004-07-21T00:00:00Z","timestamp":1090368000000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2004,1,21]]},"abstract":"<jats:p>Menthol and many of its derivatives produce profound sensory and mental effects. The receptor for menthol has been cloned and named cold- and menthol-sensitive receptor-1 (CMR1) or transient receptor potential channel M8 (TRPM8) receptor. Using a dorsal root ganglion (DRG) and dorsal horn (DH) coculture system as a model for the first sensory synapse in the CNS, we studied menthol effects on sensory synaptic transmission and the underlying mechanisms. We found that menthol increased the frequency of miniature EPSCs (mEPSCs). The effects persisted under an extracellular Ca<jats:sup>2+<\/jats:sup>-free condition but were abolished by intracellular BAPTA and pretreatment with thapsigargin. Menthol-induced increases of mEPSC frequency were blocked by 2-aminoethoxydiphenylborane (2-APB) but not affected by the phospholipase C inhibitor U73122 or by the cADP receptor inhibitor 8-bromo-cADPR (8Br-cADPR). Double-patch recordings from DRG-DH pairs showed that menthol could potentiate evoked EPSCs (eEPSCs) and change the paired-pulse ratio of eEPSCs. A Ca<jats:sup>2+<\/jats:sup>imaging study on DRG neurons demonstrated that menthol could directly release Ca<jats:sup>2+<\/jats:sup>from intracellular Ca<jats:sup>2+<\/jats:sup>stores. Menthol-induced Ca<jats:sup>2+<\/jats:sup>release was abolished by 2-APB but not affected by U73122 or 8Br-cADPR. Taken together, our results indicate that menthol can act directly on presynaptic Ca<jats:sup>2+<\/jats:sup>stores of sensory neurons to release Ca<jats:sup>2+<\/jats:sup>, resulting in a facilitation of glutamate release and a modulation of neuronal transmission at sensory synapses. Expression of TRPM8 receptor on presynaptic Ca<jats:sup>2+<\/jats:sup>stores, a novel localization for this ligand-gated ion channel, is also strongly suggested.<\/jats:p>","DOI":"10.1523\/jneurosci.4658-03.2004","type":"journal-article","created":{"date-parts":[[2004,1,21]],"date-time":"2004-01-21T19:33:07Z","timestamp":1074713587000},"page":"762-771","source":"Crossref","is-referenced-by-count":111,"title":["Menthol-Induced Ca<sup>2+<\/sup>Release from Presynaptic Ca<sup>2+<\/sup>Stores Potentiates Sensory Synaptic Transmission"],"prefix":"10.1523","volume":"24","author":[{"given":"Kenzo","family":"Tsuzuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo 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