{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:04:48Z","timestamp":1787169888196,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,3,27]],"date-time":"2014-03-27T00:00:00Z","timestamp":1395878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["HL111497"],"award-info":[{"award-number":["HL111497"]}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"crossref","award":["NRF-2010-0024258"],"award-info":[{"award-number":["NRF-2010-0024258"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Hypoxia is thought to depolarize glomus cells by inhibiting the outward K\n                            <jats:sup>+<\/jats:sup>\n                            current, which sets in motion a cascade of ionic events that lead to transmitter secretion, increased afferent carotid sinus nerve activity and increased ventilation.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Our study of Na\n                            <jats:sup>+<\/jats:sup>\n                            \u2010permeable channels in glomus cells has revealed that hypoxia not only inhibits TASK background K\n                            <jats:sup>+<\/jats:sup>\n                            channels but also indirectly activates a non\u2010selective cation channel with a single channel conductance of 20\u00a0pS. Under physiological conditions, the reversal potential of the cation channel is \u223c \u201328\u00a0mV, indicating that Na\n                            <jats:sup>+<\/jats:sup>\n                            influx is also involved in hypoxia\u2010induced excitation of glomus cells.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Activation of the 20\u00a0pS cation channel is present when the O\n                            <jats:sub>2<\/jats:sub>\n                            content is 5% or less, indicating that Na\n                            <jats:sup>+<\/jats:sup>\n                            influx occurs during moderate to severe hypoxia (&lt;5% O\n                            <jats:sub>2<\/jats:sub>\n                            ), but not mild hypoxia (&gt;5% O\n                            <jats:sub>2<\/jats:sub>\n                            ).\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            The 20\u00a0pS cation channel is directly activated by a rise in intracellular Ca\n                            <jats:sup>2+<\/jats:sup>\n                            . Thus, factors that elevate intracellular Ca\n                            <jats:sup>2+<\/jats:sup>\n                            such as hypoxia, extracellular acidosis and high external KCl all activate the cation channel. A feed\u2010forward mechanism may be present in which an initial depolarization\u2010induced rise in intracellular Ca\n                            <jats:sup>2+<\/jats:sup>\n                            opens the Na\n                            <jats:sup>+<\/jats:sup>\n                            \u2010permeable cation channel, and the Na\n                            <jats:sup>+<\/jats:sup>\n                            influx causes additional depolarization and influx of Ca\n                            <jats:sup>2+<\/jats:sup>\n                            into glomus cells.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      The current model of O\n                      <jats:sub>2<\/jats:sub>\n                      sensing by carotid body chemoreceptor (glomus) cells is that hypoxia inhibits the outward K\n                      <jats:sup>+<\/jats:sup>\n                      current and causes cell depolarization, Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx via voltage\u2010dependent Ca\n                      <jats:sup>2+<\/jats:sup>\n                      channels and a rise in intracellular [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ] ([Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      ). Here we show that hypoxia (&lt;5% O\n                      <jats:sub>2<\/jats:sub>\n                      ), in addition to inhibiting the two\u2010pore domain K\n                      <jats:sup>+<\/jats:sup>\n                      channels TASK\u20101\/3 (TASK), indirectly activates an \u223c20\u00a0pS channel in isolated glomus cells. The 20\u00a0pS channel was permeable to K\n                      <jats:sup>+<\/jats:sup>\n                      , Na\n                      <jats:sup>+<\/jats:sup>\n                      and Cs\n                      <jats:sup>+<\/jats:sup>\n                      but not to Cl\n                      <jats:sup>\u2212<\/jats:sup>\n                      or Ca\n                      <jats:sup>2+<\/jats:sup>\n                      . The 20\u00a0pS channel was not sensitive to voltage. Inhibition of TASK by external acid, depolarization of glomus cells with high external KCl (20\u00a0m\n                      <jats:sc>m<\/jats:sc>\n                      ) or opening of the Ca\n                      <jats:sup>2+<\/jats:sup>\n                      channel with FPL64176 activated the 20\u00a0pS channel when 1\u00a0m\n                      <jats:sc>m<\/jats:sc>\n                      Ca\n                      <jats:sup>2+<\/jats:sup>\n                      was present in the external solution. Ca\n                      <jats:sup>2+<\/jats:sup>\n                      (10\u00a0\u03bc\n                      <jats:sc>m<\/jats:sc>\n                      ) applied to the cytosolic side of inside\u2010out patches activated the 20\u00a0pS channel. The threshold [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      for activation of the 20\u00a0pS channel in cell\u2010attached patches was \u223c200\u00a0n\n                      <jats:sc>m<\/jats:sc>\n                      . The reversal potential of the 20\u00a0pS channel was estimated to be \u221228\u00a0mV. Our results reveal a sequential mechanism in which hypoxia (&lt;5% O\n                      <jats:sub>2<\/jats:sub>\n                      ) first inhibits the K\n                      <jats:sup>+<\/jats:sup>\n                      conductance and then activates a Na\n                      <jats:sup>+<\/jats:sup>\n                      \u2010permeable, non\u2010selective cation channel via depolarization\u2010induced rise in [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      . Our results suggest that inhibition of K\n                      <jats:sup>+<\/jats:sup>\n                      efflux and stimulation of Na\n                      <jats:sup>+<\/jats:sup>\n                      influx both contribute to the depolarization of glomus cells during moderate to severe hypoxia.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jphysiol.2013.266957","type":"journal-article","created":{"date-parts":[[2014,3,3]],"date-time":"2014-03-03T23:29:38Z","timestamp":1393889378000},"page":"1975-1992","source":"Crossref","is-referenced-by-count":28,"title":["Increase in cytosolic Ca\n                    <sup>2+<\/sup>\n                    produced by hypoxia and other depolarizing stimuli activates a non\u2010selective cation channel in chemoreceptor cells of rat carotid body"],"prefix":"10.1113","volume":"592","author":[{"given":"Dawon","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics Chicago Medical School Rosalind Franklin University of Medicine and Science  3333 Green Bay Road North Chicago IL 60064 USA"},{"name":"Department of Physiology and Institute of Health Sciences Gyeongsang National University School of Medicine  90 Chilam Jinju 660\u2010751 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaju","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Chicago Medical School Rosalind Franklin University of Medicine and Science  3333 Green Bay Road North Chicago IL 60064 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James O.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Chicago Medical School Rosalind Franklin University of Medicine and Science  3333 Green Bay Road North Chicago IL 60064 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