{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:04:19Z","timestamp":1761059059382},"reference-count":0,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1999,1,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic dietary K<jats:sup>+<\/jats:sup> loading increases the abundance of large conductance (210 pS) apical K<jats:sup>+<\/jats:sup> channels in surface cells of rat distal colon, resulting in enhanced K<jats:sup>+<\/jats:sup> secretion in this epithelium. However, the factors involved in the regulation of these K<jats:sup>+<\/jats:sup> channels are at present unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To evaluate the effect of dietary K<jats:sup>+<\/jats:sup> loading on intracellular pH and its relation to large conductance apical K<jats:sup>+<\/jats:sup> channel activity in surface cells of rat distal colon.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods\/Results<\/jats:title><jats:p>As assessed by fluorescent imaging, intracellular pH was higher in K<jats:sup>+<\/jats:sup> loaded animals (7.48 (0.09)) than in controls (7.07 (0.04); p&lt;0.01) when surface cells were bathed in NaCl solution, and a similar difference in intracellular pH was observed when cells were bathed in Na<jats:sub>2<\/jats:sub>SO<jats:sub>4<\/jats:sub> solution (7.67 (0.09) and 6.92 (0.05) respectively; p&lt;0.001). Ethylisopropylamiloride (EIPA; an inhibitor of Na<jats:sup>+<\/jats:sup>-H<jats:sup>+<\/jats:sup> exchange; 1 \u03bcM) decreased intracellular pH when surface cells from K<jats:sup>+<\/jats:sup> loaded animals were bathed in either solution, although the decrease was greater when the solution contained NaCl (\u0394pH 0.50 (0.03)) rather than Na<jats:sub>2<\/jats:sub>SO<jats:sub>4<\/jats:sub> (\u0394pH 0.18 (0.02); p&lt;0.05). In contrast, EIPA had no effect in cells from control animals. As assessed by patch clamp recording techniques, the activity of large conductance K<jats:sup>+<\/jats:sup> channels in excised inside-out membrane patches from distal colonic surface cells of K<jats:sup>+<\/jats:sup> loaded animals increased twofold when the bath pH was raised from 7.40 to 7.60. As assessed by cell attached patches in distal colonic surface cells from K<jats:sup>+<\/jats:sup> loaded animals, the addition of 1 \u03bcM EIPA decreased K<jats:sup>+<\/jats:sup> channel activity by 50%, consistent with reversal of Na<jats:sup>+<\/jats:sup>-H<jats:sup>+<\/jats:sup> exchange mediated intracellular alkalinisation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Intracellular alkalinisation stimulates pH sensitive large conductance apical K<jats:sup>+<\/jats:sup> channels in rat distal colonic surface cells as part of the K<jats:sup>+<\/jats:sup> secretory response to chronic dietary K<jats:sup>+<\/jats:sup>loading. Intracellular alkalinisation seems to reflect an increase in EIPA sensitive Na<jats:sup>+<\/jats:sup>-H<jats:sup>+<\/jats:sup> exchange, which may be a manifestation of the secondary hyperaldosteronism associated with this model of colonic K<jats:sup>+<\/jats:sup> adaptation.<\/jats:p><\/jats:sec>","DOI":"10.1136\/gut.44.1.40","type":"journal-article","created":{"date-parts":[[2010,6,30]],"date-time":"2010-06-30T16:46:12Z","timestamp":1277916372000},"page":"40-46","source":"Crossref","is-referenced-by-count":13,"title":["Potassium secretion in rat distal colon during dietary potassium loading: role of pH regulated apical potassium channels"],"prefix":"10.1136","volume":"44","author":[{"given":"G I","family":"Sandle","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Butterfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1999,1,1]]},"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.44.1.40","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T03:34:29Z","timestamp":1601091269000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.44.1.40"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,1,1]]},"references-count":0,"journal-issue":{"issue":"1","published-online":{"date-parts":[[1999,1,1]]},"published-print":{"date-parts":[[1999,1,1]]}},"alternative-id":["10.1136\/gut.44.1.40"],"URL":"https:\/\/doi.org\/10.1136\/gut.44.1.40","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"value":"0017-5749","type":"print"},{"value":"1468-3288","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,1,1]]}}}