{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:38:31Z","timestamp":1790642311999,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2017,12,28]],"date-time":"2017-12-28T00:00:00Z","timestamp":1514419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL\u2010111497"],"award-info":[{"award-number":["HL\u2010111497"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,8]]},"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                            We studied the role of the large\u2010conductance Ca\n                            <jats:sup>2+<\/jats:sup>\n                            \u2010activated K\n                            <jats:sup>+<\/jats:sup>\n                            channel (BK) and voltage\u2010dependent K\n                            <jats:sup>+<\/jats:sup>\n                            channels (Kv) on [Ca\n                            <jats:sup>2+<\/jats:sup>\n                            ]\n                            <jats:sub>i<\/jats:sub>\n                            responses to a wide range of hypoxia at different resting cell membrane potential (\n                            <jats:italic>E<\/jats:italic>\n                            <jats:sub>m<\/jats:sub>\n                            ).\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            BK\/Kv were mostly closed at rest in normoxia. BK\/Kv became basally active when cells were depolarized by elevated [KCl]\n                            <jats:sub>o<\/jats:sub>\n                            (&gt;12\u00a0m\n                            <jats:sc>m<\/jats:sc>\n                            ). Regardless of whether BK\/Kv were closed or basally open, hypoxia\u2010induced elevation of [Ca\n                            <jats:sup>2+<\/jats:sup>\n                            ]\n                            <jats:sub>i<\/jats:sub>\n                            was enhanced 2\u2010 to 3\u2010fold by inhibitors of BK\/Kv.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Hypoxia\u2010induced elevation of [Ca\n                            <jats:sup>2+<\/jats:sup>\n                            ]\n                            <jats:sub>i<\/jats:sub>\n                            was enhanced \u223c2\u2010fold by an inhibitor of Kv2, a major Kv in rat glomus cells.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Hypoxia did not inhibit BK in inside\u2010out patches.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Our study supports a scheme in which activation of BK\/Kv strongly limits the magnitude of hypoxia\u2010induced [Ca\n                            <jats:sup>2+<\/jats:sup>\n                            ]\n                            <jats:sub>i<\/jats:sub>\n                            rise, with Kv having a much greater effect than BK.\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                      Large\u2010conductance K\n                      <jats:sub>Ca<\/jats:sub>\n                      (BK) and other voltage\u2010dependent K\n                      <jats:sup>+<\/jats:sup>\n                      channels (Kv) are highly expressed in carotid body (CB) glomus cells, but their role in hypoxia\u2010induced excitation is still not well defined and remains controversial. We addressed this issue by studying the effects of inhibitors of BK (IBTX) and BK\/Kv (TEA\/4\u2010AP) on [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      responses to a wide range of hypoxia at different levels of resting cell membrane potential (\n                      <jats:italic>E<\/jats:italic>\n                      <jats:sub>m<\/jats:sub>\n                      ). IBTX and TEA\/4\u2010AP did not affect the basal [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      in isolated glomus cells bathed in 5\u00a0m\n                      <jats:sc>m<\/jats:sc>\n                      KCl\n                      <jats:sub>o<\/jats:sub>\n                      , but elicited transient increases in [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      in cells that were moderately depolarized (11\u201320\u00a0mV) by elevation of [KCl]\n                      <jats:sub>o<\/jats:sub>\n                      (12\u201320\u00a0m\n                      <jats:sc>m<\/jats:sc>\n                      ). Thus, BK and Kv were mostly closed at rest and activated by depolarization. Four different levels of hypoxia (mild, moderate, severe, anoxia) were used to produce a wide range of [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      elevation (0\u2013700\u00a0n\n                      <jats:sc>m<\/jats:sc>\n                      ). IBTX did not affect the rise in [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      , but TEA\/4\u2010AP strongly (\u223c3\u2010fold) enhanced [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      rise by moderate and severe levels of hypoxia. Guangxitoxin, a Kv2 blocker, inhibited the whole\u2010cell current by \u223c50%, and enhanced 2\u2010fold the [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      rise elicited by moderate and severe levels of hypoxia. Anoxia did not directly affect BK, but activated BK via depolarization. Our findings do not support the view that hypoxia inhibits BK\/Kv to initiate or maintain the hypoxic response. Rather, our results show that BK\/Kv are activated as glomus cells depolarize in response to hypoxia, which then limits the rise in [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      . Inhibition of Kv may provide a mechanism to enhance the chemosensory activity of the CB and ventilation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp275275","type":"journal-article","created":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T06:23:10Z","timestamp":1511245390000},"page":"3119-3136","source":"Crossref","is-referenced-by-count":21,"title":["Activation of voltage\u2010dependent K\n                    <sup>+<\/sup>\n                    channels strongly limits hypoxia\u2010induced elevation of [Ca\n                    <sup>2+<\/sup>\n                    ]\n                    <sub>i<\/sub>\n                    in rat carotid body glomus cells"],"prefix":"10.1113","volume":"596","author":[{"given":"Jiaju","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Chicago Medical School Rosalind Franklin University of Medicine and Science  North Chicago IL 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