{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T16:48:04Z","timestamp":1749660484949,"version":"3.40.5"},"reference-count":32,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2015,1,15]]},"abstract":"<jats:p>Arterial blood O<jats:sub>2<\/jats:sub>levels are detected by specialized sensory organs called carotid bodies. Voltage-gated Ca<jats:sup>2+<\/jats:sup>channels (VGCCs) are important for carotid body O<jats:sub>2<\/jats:sub>sensing. Given that T-type VGCCs contribute to nociceptive sensation, we hypothesized that they participate in carotid body O<jats:sub>2<\/jats:sub>sensing. The rat carotid body expresses high levels of mRNA encoding the \u03b1<jats:sub>1H<\/jats:sub>-subunit, and \u03b1<jats:sub>1H<\/jats:sub>protein is localized to glomus cells, the primary O<jats:sub>2<\/jats:sub>-sensing cells in the chemoreceptor tissue, suggesting that Ca<jats:sub>V<\/jats:sub>3.2 is the major T-type VGCC isoform expressed in the carotid body. Mibefradil and TTA-A2, selective blockers of the T-type VGCC, markedly attenuated elevation of hypoxia-evoked intracellular Ca<jats:sup>2+<\/jats:sup>concentration, secretion of catecholamines from glomus cells, and sensory excitation of the rat carotid body. Similar results were obtained in the carotid body and glomus cells from Ca<jats:sub>V<\/jats:sub>3.2 knockout ( Cacna1h<jats:sup>\u2212\/\u2212<\/jats:sup>) mice. Since cystathionine-\u03b3-lyase (CSE)-derived H<jats:sub>2<\/jats:sub>S is a critical mediator of the carotid body response to hypoxia, the role of T-type VGCCs in H<jats:sub>2<\/jats:sub>S-mediated O<jats:sub>2<\/jats:sub>sensing was examined. Like hypoxia, NaHS, a H<jats:sub>2<\/jats:sub>S donor, increased intracellular Ca<jats:sup>2+<\/jats:sup>concentration and augmented carotid body sensory nerve activity in wild-type mice, and these effects were markedly attenuated in Cacna1h<jats:sup>\u2212\/\u2212<\/jats:sup>mice. In wild-type mice, TTA-A2 markedly attenuated glomus cell and carotid body sensory nerve responses to hypoxia, and these effects were absent in CSE knockout mice. These results demonstrate that Ca<jats:sub>V<\/jats:sub>3.2 T-type VGCCs contribute to the H<jats:sub>2<\/jats:sub>S-mediated carotid body response to hypoxia.<\/jats:p>","DOI":"10.1152\/ajpcell.00141.2014","type":"journal-article","created":{"date-parts":[[2014,11,7]],"date-time":"2014-11-07T08:50:29Z","timestamp":1415350229000},"page":"C146-C154","source":"Crossref","is-referenced-by-count":19,"title":["Ca<sub>V<\/sub>3.2 T-type Ca<sup>2+<\/sup>channels in H<sub>2<\/sub>S-mediated hypoxic response of the carotid body"],"prefix":"10.1152","volume":"308","author":[{"given":"Vladislav V.","family":"Makarenko","sequence":"first","affiliation":[{"name":"Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, The University of Chicago, Chicago, Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Jie","family":"Peng","sequence":"additional","affiliation":[{"name":"Institute for Integrative Physiology and Center for Systems Biology of O2 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