{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:58:22Z","timestamp":1790996302289,"version":"4.1.0"},"reference-count":46,"publisher":"American Physiological Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2012,5,15]]},"abstract":"<jats:p> Little is known about the role of Ca<jats:sup>2+<\/jats:sup> in central chemosensitive signaling. We use electrophysiology to examine the chemosensitive responses of tetrodotoxin (TTX)-insensitive oscillations and spikes in neurons of the locus ceruleus (LC), a chemosensitive region involved in respiratory control. We show that both TTX-insensitive spikes and oscillations in LC neurons are sensitive to L-type Ca<jats:sup>2+<\/jats:sup> channel inhibition and are activated by increased CO<jats:sub>2<\/jats:sub>\/H<jats:sup>+<\/jats:sup>. Spikes appear to arise from L-type Ca<jats:sup>2+<\/jats:sup> channels on the soma whereas oscillations arise from L-type Ca<jats:sup>2+<\/jats:sup> channels that are distal to the soma. In HEPES-buffered solution (nominal absence of CO<jats:sub>2<\/jats:sub>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>), acidification does not activate either oscillations or spikes. When CO<jats:sub>2<\/jats:sub> is increased while extracellular pH is held constant by elevated HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>, both oscillation and spike frequency increase. Furthermore, plots of both oscillation and spike frequency vs. intracellular [HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>]show a strong linear correlation. Increased frequency of TTX-insensitive spikes is associated with increases in intracellular Ca<jats:sup>2+<\/jats:sup> concentrations. Finally, both the appearance and frequency of TTX-insensitive spikes and oscillations increase over postnatal ages day 3\u201316. Our data suggest that 1) L-type Ca<jats:sup>2+<\/jats:sup> currents in LC neurons arise from channel populations that reside in different regions of the neuron, 2) these L-type Ca<jats:sup>2+<\/jats:sup> currents undergo significant postnatal development, and 3) the activity of these L-type Ca<jats:sup>2+<\/jats:sup> currents is activated by increased CO<jats:sub>2<\/jats:sub> through a HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>-dependent mechanism. Thus the activity of L-type Ca<jats:sup>2+<\/jats:sup> channels is likely to play a role in the chemosensitive response of LC neurons and may underlie significant changes in LC neuron chemosensitivity during neonatal development. <\/jats:p>","DOI":"10.1152\/japplphysiol.01585.2011","type":"journal-article","created":{"date-parts":[[2012,3,9]],"date-time":"2012-03-09T00:52:43Z","timestamp":1331254363000},"page":"1715-1726","source":"Crossref","is-referenced-by-count":20,"title":["Postnatal development and activation of L-type Ca<sup>2+<\/sup> currents in locus ceruleus neurons: implications for a role for Ca<sup>2+<\/sup> in central chemosensitivity"],"prefix":"10.1152","volume":"112","author":[{"given":"Ann N.","family":"Imber","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert 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