{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T10:56:58Z","timestamp":1753181818664,"version":"3.37.3"},"reference-count":36,"publisher":"American Physiological Society","issue":"3","funder":[{"DOI":"10.13039\/100000069","name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)","doi-asserted-by":"publisher","award":["AR-059397"],"award-info":[{"award-number":["AR-059397"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2016,3,1]]},"abstract":"<jats:p> The mechanisms by which G proteins modulate voltage-gated Ca<jats:sup>2+<\/jats:sup> channel currents (Ca<jats:sub>V<\/jats:sub>), particularly Ca<jats:sub>V<\/jats:sub>2.2 and Ca<jats:sub>V<\/jats:sub>2.3, are voltage dependent (VD) or voltage independent (VI). VD pathways are typically mediated by G\u03b1<jats:sub>i\/o<\/jats:sub> and G\u03b1<jats:sub>S<\/jats:sub> subfamilies. On the other hand, VI inhibition modulation is coupled to the G\u03b1<jats:sub>q<\/jats:sub> subfamily and signaling pathways downstream of phospholipase C stimulation. In most studies, this latter pathway has been shown to be linked to G\u03b1<jats:sub>q<\/jats:sub> and\/or G\u03b1<jats:sub>11<\/jats:sub> protein subunits. However, there are no studies that have examined whether natively expressed G\u03b1<jats:sub>14<\/jats:sub> subunits (G\u03b1<jats:sub>q<\/jats:sub> subfamily member) couple G protein-coupled receptors (GPCR) with Ca<jats:sub>V<\/jats:sub>2.2 channels. We report that G\u03b1<jats:sub>14<\/jats:sub> subunits functionally couple the substance P (SP)\/neurokinin-1 (NK-1) receptor pathway to Ca<jats:sub>V<\/jats:sub>2.2 channels in acutely dissociated rat celiac-superior mesenteric ganglion (CSMG) neurons. Exposure of CSMG neurons to SP blocked the Ca<jats:sub>V<\/jats:sub>2.2 currents in a predominantly VD manner that was pertussis toxin and cholera toxin resistant, as well as G\u03b1<jats:sub>q\/11<\/jats:sub> independent. However, silencing G\u03b1<jats:sub>14<\/jats:sub> subunits significantly attenuated the SP-mediated Ca<jats:sup>2+<\/jats:sup> current block. In another set of experiments, exposure of CSMG neurons to SP led to the inhibition of KCNQ K<jats:sup>+<\/jats:sup> M-currents. The SP-mediated M-current block was significantly reduced in neurons transfected with G\u03b1<jats:sub>14<\/jats:sub> small-interference RNA. Finally, overexpression of the GTP-bound G\u03b1<jats:sub>q\/11<\/jats:sub> binding protein RGS2 did not alter the block of M-currents by SP but significantly abolished the oxotremorine methiodide-mediated M-current inhibition. Taken together, these results provide evidence of a new G\u03b1<jats:sub>14<\/jats:sub>-coupled signaling pathway that modulates Ca<jats:sub>V<\/jats:sub>2.2 and M-currents via SP-stimulated NK-1 receptors in CSMG neurons. <\/jats:p>","DOI":"10.1152\/jn.00980.2015","type":"journal-article","created":{"date-parts":[[2016,2,3]],"date-time":"2016-02-03T23:04:06Z","timestamp":1454540646000},"page":"1577-1586","source":"Crossref","is-referenced-by-count":2,"title":["G\u03b1<sub>14<\/sub> subunit-mediated inhibition of voltage-gated Ca<sup>2+<\/sup> and K<sup>+<\/sup> channels via neurokinin-1 receptors in rat celiac-superior mesenteric ganglion neurons"],"prefix":"10.1152","volume":"115","author":[{"given":"Shigekazu","family":"Sugino","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Penn State College of Medicine, Hershey, 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