{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:26:19Z","timestamp":1780511179262,"version":"3.54.1"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,8,8]],"date-time":"2006-08-08T00:00:00Z","timestamp":1154995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2006,8,15]]},"abstract":"<jats:p>The O<jats:sub>2<\/jats:sub> dependence of ouabain\u2010independent K<jats:sup>+<\/jats:sup> transport mechanisms has been studied by unidirectional Rb<jats:sup>+<\/jats:sup> flux analysis in crucian carp red blood cells (RBCs). The following observations suggest that O<jats:sub>2<\/jats:sub> activates K<jats:sup>+<\/jats:sup>\u2013Cl<jats:sup>\u2212<\/jats:sup> cotransport (KCC) and deactivates Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup>\u20132Cl<jats:sup>\u2212<\/jats:sup> cotransport (NKCC) in these cells via separate O<jats:sub>2<\/jats:sub> sensors that differ in their O<jats:sub>2<\/jats:sub> affinity. When O<jats:sub>2<\/jats:sub> tension (<jats:italic>P<\/jats:italic><jats:sub>O2<\/jats:sub>) at physiological pH 7.9 was increased from 0 to 1, 4, 21 or 100 kPa, K<jats:sup>+<\/jats:sup> (Rb<jats:sup>+<\/jats:sup>) influx was increasingly inhibited, and at 100 kPa amounted to about 30% of the value at 0 kPa. This influx was almost completely Cl<jats:sup>\u2212<\/jats:sup> dependent at high and low <jats:italic>P<\/jats:italic><jats:sub>O2<\/jats:sub>, as shown by substituting Cl<jats:sup>\u2212<\/jats:sup> with nitrate or methanesulphonate. K<jats:sup>+<\/jats:sup> (Rb<jats:sup>+<\/jats:sup>) efflux showed a similar <jats:italic>P<\/jats:italic><jats:sub>O2<\/jats:sub> dependence as K<jats:sup>+<\/jats:sup> (Rb<jats:sup>+<\/jats:sup>) influx, but was about 4\u20135 times higher over the whole <jats:italic>P<\/jats:italic><jats:sub>O2<\/jats:sub> range. The combined net free energy of transmembrane ion gradients favoured net efflux of ions for both KCC and NKCC mechanisms. The KCC inhibitor dihydroindenyloxyalkanoic acid (DIOA, 0.1 m<jats:sc>m<\/jats:sc>) abolished Cl<jats:sup>\u2212<\/jats:sup>\u2010dependent K<jats:sup>+<\/jats:sup> (Rb<jats:sup>+<\/jats:sup>) influx at a <jats:italic>P<\/jats:italic><jats:sub>O2<\/jats:sub> of 100 kPa, but was only partially effective at low <jats:italic>P<\/jats:italic><jats:sub>O2<\/jats:sub> (0\u20131 kPa). At <jats:italic>P<\/jats:italic><jats:sub>O2<\/jats:sub> values between 0 and 4 kPa, K<jats:sup>+<\/jats:sup> (Rb<jats:sup>+<\/jats:sup>) influx was further unaffected by variations in pH between 8.4 and 6.9, whereas the flux at 21 and 100 kPa was strongly reduced by pH values below 8.4. At pH 8.4, where K<jats:sup>+<\/jats:sup> (Rb<jats:sup>+<\/jats:sup>) influx was maximal at high and low <jats:italic>P<\/jats:italic><jats:sub>O2<\/jats:sub>, titration of K<jats:sup>+<\/jats:sup> (Rb<jats:sup>+<\/jats:sup>) influx with the NKCC inhibitor bumetanide (1, 10 and 100 \u03bc<jats:sc>m<\/jats:sc>) revealed a highly bumetanide\u2010sensitive K<jats:sup>+<\/jats:sup> (Rb<jats:sup>+<\/jats:sup>) flux pathway at low <jats:italic>P<\/jats:italic><jats:sub>O2<\/jats:sub>, and a relative bumetanide\u2010insensitive pathway at high <jats:italic>P<\/jats:italic><jats:sub>O2<\/jats:sub>. The bumetanide\u2010sensitive K<jats:sup>+<\/jats:sup> (Rb<jats:sup>+<\/jats:sup>) influx pathway was activated by decreasing <jats:italic>P<\/jats:italic><jats:sub>O2<\/jats:sub>, with a <jats:italic>P<\/jats:italic><jats:sub>O2<\/jats:sub> for half\u2010maximal activation (<jats:italic>P<\/jats:italic><jats:sub>50<\/jats:sub>) not significantly different from the <jats:italic>P<\/jats:italic><jats:sub>50<\/jats:sub> for haemoglobin O<jats:sub>2<\/jats:sub> binding. The bumetanide\u2010insensitive K<jats:sup>+<\/jats:sup> (Rb<jats:sup>+<\/jats:sup>) influx pathway was activated by increasing <jats:italic>P<\/jats:italic><jats:sub>O2<\/jats:sub> with a <jats:italic>P<\/jats:italic><jats:sub>50<\/jats:sub> significantly higher than for haemoglobin O<jats:sub>2<\/jats:sub> binding. These results are relevant for the pathologically altered O<jats:sub>2<\/jats:sub> sensitivity of RBC ion transport in certain human haemoglobinopathies.<\/jats:p>","DOI":"10.1113\/jphysiol.2006.112680","type":"journal-article","created":{"date-parts":[[2006,6,9]],"date-time":"2006-06-09T00:48:04Z","timestamp":1149814084000},"page":"37-48","source":"Crossref","is-referenced-by-count":13,"title":["Two different oxygen sensors regulate oxygen\u2010sensitive K<sup>+<\/sup> transport in crucian carp red blood 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