{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T03:39:00Z","timestamp":1773459540855,"version":"3.50.1"},"reference-count":31,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[1999,1,1]]},"abstract":"<jats:p> Overholt, Jeffrey L. and Nanduri R. Prabhakar. Norepinephrine inhibits a toxin resistant Ca<jats:sup>2+<\/jats:sup> current in carotid body glomus cells: evidence for a direct G protein mechanism. J. Neurophysiol. 81: 225\u2013233, 1999. Previous studies have demonstrated that endogenous norepinephrine (NE) inhibits carotid body (CB) sensory discharge, and the cellular actions of NE have been associated with inhibition of Ca<jats:sup>2+<\/jats:sup> current in glomus cells. The purpose of the present study was to elucidate the characteristics and mechanism of NE inhibition of whole cell Ca<jats:sup>2+<\/jats:sup> current isolated from rabbit CB glomus cells and to determine the type(s) of Ca<jats:sup>2+<\/jats:sup> channel involved. NE (10 \u03bcM) inhibited 24 \u00b1 2% (SE) of the macroscopic Ca<jats:sup>2+<\/jats:sup> current measured at the end of a 25 ms pulse to 0 mV and slowed activation of the current. The \u03b1<jats:sub>2<\/jats:sub> adrenergic receptor antagonist, SK&amp;F 86466, attenuated these effects. Inhibition by NE was fast and voltage-dependent i.e., maximal at \u221210 mV and then diminished with stronger depolarizations. This is characteristic of G protein \u03b2\u03b3 subunit interaction with the \u03b1<jats:sub>1<\/jats:sub> subunit of certain Ca<jats:sup>2+<\/jats:sup> channels, which can be relieved by depolarizing steps. A depolarizing step (30 ms to +80 mV) significantly increased (14 \u00b1 1%) current in the presence of NE, whereas it had no effect before application of NE (1 \u00b1 1%). To further test for the involvement of G proteins, NE was applied to cells where intracellular GTP was replaced by GDP-\u03b2S. NE had little or no effect on Ca<jats:sup>2+<\/jats:sup> current in cells dialyzed with GDP-\u03b2S. To determine whether NE was inhibiting N- and\/or P\/Q-type channels, we applied NE in the presence of \u03c9-conotoxin MVIIC (MVIIC). In the presence of 2.5 \u03bcM MVIIC, NE was equally potent at inhibiting the Ca<jats:sup>2+<\/jats:sup> current (23 \u00b1 4% vs. 23 \u00b1 4% in control), suggesting that NE was not exclusively inhibiting N- or P\/Q-type channels. NE was also equally potent (30 \u00b1 2% vs. 26 \u00b1 4% in control) at inhibiting the Ca<jats:sup>2+<\/jats:sup> current in the presence of 2 \u03bcM nisoldipine, suggesting that NE was not inhibiting L-type channels. Further, NE inhibited a significantly larger proportion (47 \u00b1 6%) of the resistant Ca<jats:sup>2+<\/jats:sup> current remaining in the presence of NISO and MVIIC. These results suggest that NE inhibition of Ca<jats:sup>2+<\/jats:sup> current in rabbit CB glomus cells is mediated in most part by effects on the resistant, non L-, N-, or P\/Q-type channel and involves a direct G protein \u03b2\u03b3 interaction with this channel. <\/jats:p>","DOI":"10.1152\/jn.1999.81.1.225","type":"journal-article","created":{"date-parts":[[2017,12,25]],"date-time":"2017-12-25T04:58:37Z","timestamp":1514177917000},"page":"225-233","source":"Crossref","is-referenced-by-count":21,"title":["Norepinephrine Inhibits a Toxin Resistant Ca<sup>2+<\/sup> Current in Carotid Body Glomus Cells: Evidence for a Direct G Protein Mechanism"],"prefix":"10.1152","volume":"81","author":[{"given":"Jeffrey L.","family":"Overholt","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4970"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanduri R.","family":"Prabhakar","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4970"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/340153a0"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp021956"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-11-07067.1994"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/385446a0"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.003bx.x"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp021083"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1993.70.4.1378"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/BF00656997"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/380258a0"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(94)90157-0"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/380255a0"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s002329900153"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(91)90054-M"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.5.2507"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.107.1.133"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(92)90260-9"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1997.78.5.2467"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(96)00832-3"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1992.0059"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(89)90191-8"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-08-02339.1991"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-2572-1_6"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(94)90048-5"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90132-7"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.16.8866"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1124\/mol.52.2.282"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.21.10208"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-2966-8_14"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-19-06000.1996"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-05-01625.1997"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80229-9"}],"container-title":["Journal of Neurophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/jn.1999.81.1.225","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T04:25:11Z","timestamp":1568003111000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/jn.1999.81.1.225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,1,1]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1999,1,1]]}},"alternative-id":["10.1152\/jn.1999.81.1.225"],"URL":"https:\/\/doi.org\/10.1152\/jn.1999.81.1.225","relation":{},"ISSN":["0022-3077","1522-1598"],"issn-type":[{"value":"0022-3077","type":"print"},{"value":"1522-1598","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,1,1]]}}}