{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:39:19Z","timestamp":1790642359250,"version":"4.1.0"},"reference-count":35,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2002,8,1]]},"abstract":"<jats:p> The carotid bodies respond to changes in arterial O<jats:sub>2<\/jats:sub>, CO<jats:sub>2<\/jats:sub>, and pH, and Ca<jats:sup>2+<\/jats:sup> influx via voltage-gated Ca<jats:sup>2+<\/jats:sup> channels is an important step in the chemoreception process. The objectives of the present study were as follows: 1) to determine whether hypercapnia modulates Ca<jats:sup>2+<\/jats:sup> current in glomus cells, and if so, to determine if this modulation is secondary to changes in pH; 2) to examine the mechanism of CO<jats:sub>2<\/jats:sub>modulation of the Ca<jats:sup>2+<\/jats:sup> current; and 3) to determine whether the effects of hypercapnia and hypoxia on Ca<jats:sup>2+<\/jats:sup> channel activity in glomus cells are synergistic. The effects of CO<jats:sub>2<\/jats:sub> on Ca<jats:sup>2+<\/jats:sup> current were monitored in glomus cells isolated from rabbit carotid bodies using both perforated and conventional patch-clamp techniques. Raising CO<jats:sub>2<\/jats:sub>in the extracellular solution from 5 to 10% (hypercapnia) reversibly augmented the whole-cell Ca<jats:sup>2+<\/jats:sup> current. This augmentation was rapid and increased the whole-cell Ca<jats:sup>2+<\/jats:sup> current similarly in both the perforated and the conventional patch configurations by 16 \u00b1 2% ( n = 5) and 15 \u00b1 1% ( n = 32), respectively. The following observations suggest that the effects of CO<jats:sub>2<\/jats:sub> are not secondary to changes in pH: 1) isohydric hypercapnia (pH maintained at 7.4) augmented the Ca<jats:sup>2+<\/jats:sup> current by 24 \u00b1 2% ( n = 6); 2) decreasing the pH of the extra- or intracellular solutions decreased the Ca<jats:sup>2+<\/jats:sup>current by 43 \u00b1 4% ( n = 8) and 13 \u00b1 1% ( n = 5), respectively; and 3) hypercapnia did not shift the half-maximal activation voltage ( V <jats:sub>1\/2<\/jats:sub>), whereas intracellular and extracellular acidosis alone caused shifts in V <jats:sub>1\/2<\/jats:sub>. Furthermore, 100 nM of a membrane-permeable protein kinase A inhibitor prevented the augmentation by CO<jats:sub>2<\/jats:sub>, and 500 \u03bcM 8-Br-cAMP mimicked the effect of CO<jats:sub>2<\/jats:sub> by augmenting the Ca<jats:sup>2+<\/jats:sup> current by 10 \u00b1 2% ( n= 6). Also, cyclic AMP levels in carotid bodies increased from 1.98 \u00b1 0.6 to 9.0 \u00b1 2 pmol\/\u03bcg protein in response to hypercapnia. In contrast, decreasing pH in the nominal absence of CO<jats:sub>2<\/jats:sub> did not affect cAMP levels in rabbit carotid bodies. Further, nisoldipine, but not \u03c9-conotoxin MVIIC, prevented augmentation of the Ca<jats:sup>2+<\/jats:sup> current by CO<jats:sub>2<\/jats:sub>. In addition, when combined, hypercapnia and hypoxia augmented the Ca<jats:sup>2+<\/jats:sup> current by 26 \u00b1 4% ( n = 7), which is greater than either stimulus alone, suggesting the effects are additive. Taken together, these results indicate that L-type Ca<jats:sup>2+<\/jats:sup> current is augmented by hypercapnia. The effect of CO<jats:sub>2<\/jats:sub> is not secondary to changes in pH and seems to be mediated by a protein kinase A-dependent mechanism. Furthermore, hypercapnia and hypoxia act additively in stimulating Ca<jats:sup>2+<\/jats:sup> current in glomus cells. <\/jats:p>","DOI":"10.1152\/jn.2002.88.2.604","type":"journal-article","created":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T14:55:37Z","timestamp":1513868137000},"page":"604-612","source":"Crossref","is-referenced-by-count":58,"title":["CO<sub>2<\/sub> and pH Independently Modulate L-Type Ca<sup>2+<\/sup> Current in Rabbit Carotid Body Glomus Cells"],"prefix":"10.1152","volume":"88","author":[{"given":"Beth A.","family":"Summers","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Overholt","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 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