{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T18:35:33Z","timestamp":1780684533640,"version":"3.54.1"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2001,8,31]]},"abstract":"<jats:p>\n            Hypoxic inhibition of large-conductance Ca\n            <jats:sup>2+<\/jats:sup>\n            -dependent K\n            <jats:sup>+<\/jats:sup>\n            channels (maxiK) of rat carotid body type I cells is a well-established fact. However, the molecular mechanisms of such inhibition and the role of these channels in the process of hypoxic transduction remain unclear. We have examined the mechanisms of interaction of O\n            <jats:sub>2<\/jats:sub>\n            with maxiK channels exploring the effect of hypoxia on maxiK currents recorded with the whole-cell and the inside-out configuration of the patch-clamp technique. Hypoxia inhibits channel activity both in whole-cell and in excised membrane patches. This effect is strongly voltage- and Ca\n            <jats:sup>2+<\/jats:sup>\n            -dependent, being maximal at low [Ca\n            <jats:sup>2+<\/jats:sup>\n            ] and low membrane potential. The analysis of single-channel kinetics reveals a gating scheme comprising three open and five closed states. Hypoxia inhibits channel activity increasing the time the channel spends in the longest closed states, an effect that could be explained by a decrease in the Ca\n            <jats:sup>2+<\/jats:sup>\n            sensitivity of those closed states. Reducing maxiK channels with dithiothreitol (DTT) increases channel open probability, whereas oxidizing the channels with 2,2\u2032-dithiopyridine (DTDP) has the opposite effect. These results suggest that hypoxic inhibition is not related with a reduction of channel thiol groups. However, CO, a competitive inhibitor of O\n            <jats:sub>2<\/jats:sub>\n            binding to hemoproteins, fully reverts hypoxic inhibition, both at the whole-cell and the single-channel level. We conclude that O\n            <jats:sub>2<\/jats:sub>\n            interaction with maxiK channels does not require cytoplasmic mediators. Such interaction could be mediated by a membrane hemoprotein that, as an O\n            <jats:sub>2<\/jats:sub>\n            sensor, would modulate channel activity.\n          <\/jats:p>","DOI":"10.1161\/hh1701.095632","type":"journal-article","created":{"date-parts":[[2007,9,28]],"date-time":"2007-09-28T18:32:49Z","timestamp":1191004369000},"page":"430-436","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":136,"title":["O\n            <sub>2<\/sub>\n            Modulates Large-Conductance Ca\n            <sup>2+<\/sup>\n            -Dependent K\n            <sup>+<\/sup>\n            Channels of Rat Chemoreceptor Cells by a Membrane-Restricted and CO-Sensitive Mechanism"],"prefix":"10.1161","volume":"89","author":[{"given":"A. M.","family":"Riesco-Fagundo","sequence":"first","affiliation":[{"name":"From the Instituto de Biologi\u0301a y Gene\u0301tica Molecular (IBGM), Universidad de Valladolid y Consejo superior de investigaciones cienti\u0301ficas (CSIC), Dpto de Bioqui\u0301mica y Biologi\u0301a Molecular y Fisiologi\u0301a, Facultad de Medicina, Valladolid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. T.","family":"Pe\u0301rez-Garci\u0301a","sequence":"additional","affiliation":[{"name":"From the Instituto de Biologi\u0301a y Gene\u0301tica Molecular (IBGM), Universidad de Valladolid y Consejo superior de investigaciones cienti\u0301ficas (CSIC), Dpto de Bioqui\u0301mica y Biologi\u0301a Molecular y Fisiologi\u0301a, Facultad de Medicina, Valladolid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Gonza\u0301lez","sequence":"additional","affiliation":[{"name":"From the Instituto de Biologi\u0301a y Gene\u0301tica Molecular (IBGM), Universidad de Valladolid y Consejo superior de investigaciones cienti\u0301ficas (CSIC), Dpto de Bioqui\u0301mica y Biologi\u0301a Molecular y Fisiologi\u0301a, Facultad de Medicina, Valladolid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. R.","family":"Lo\u0301pez-Lo\u0301pez","sequence":"additional","affiliation":[{"name":"From the Instituto de Biologi\u0301a y Gene\u0301tica Molecular (IBGM), Universidad de Valladolid y Consejo superior de investigaciones cienti\u0301ficas (CSIC), Dpto de Bioqui\u0301mica y Biologi\u0301a Molecular y Fisiologi\u0301a, Facultad de Medicina, Valladolid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1994.74.4.829"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.100.3.427"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020606"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00135.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.63.1.259"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1994.tb55698.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/352711a0"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00373904"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.110.1.35"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-13-04942.1997"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.113.6.897"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp022044"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(92)80126-2"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp021939"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(96)79568-1"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1997.0054"},{"key":"e_1_3_3_17_2","first-page":"870","volume":"12","year":"1992","unstructured":"Schoenmakers JM, Visser GJ, Flik G, Theuvenet APR. 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