{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T17:01:31Z","timestamp":1773421291356,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,11,23]],"date-time":"2004-11-23T00:00:00Z","timestamp":1101168000000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:p>Exercise\u2010induced loss of skeletal muscle K<jats:sup>+<\/jats:sup> can seriously impede muscle performance through membrane depolarization. Thus far, it has been assumed that the negative equilibrium potential and large membrane conductance of Cl<jats:sup>\u2212<\/jats:sup> attenuate the loss of force during hyperkalaemia. We questioned this idea because there is some evidence that Cl<jats:sup>\u2212<\/jats:sup> itself can exert a depolarizing influence on membrane potential (<jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub>). With this study we tried to identify the possible roles played by Cl<jats:sup>\u2212<\/jats:sup> during hyperkalaemia. Isolated rat soleus muscles were kept at 25 \u00b0C and twitch contractions were evoked by current pulses. Reducing [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>o<\/jats:sub> to 5 m<jats:sc>m<\/jats:sc>, prior to introducing 12.5 m<jats:sc>m<\/jats:sc> K<jats:sub>o<\/jats:sub>, prevented the otherwise occurring loss of force. Reversing the order of introducing these two solutions revealed an additional effect, i.e. the ongoing hyperkalaemia\u2010related loss of force was sped up tenfold after reducing [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>o<\/jats:sub>. However, hereafter twitch force recovered completely. The recovery of force was absent at [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub> exceeding 14 m<jats:sc>m<\/jats:sc>. In addition, reducing [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>o<\/jats:sub> increased membrane excitability by 24%, as shown by a shift in the relationship between force and current level. Measurements of <jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub> indicated that the antagonistic effect of reducing [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>o<\/jats:sub> on hyperkalaemia\u2010induced loss of force was due to low\u2010Cl<jats:sup>\u2212<\/jats:sup>\u2010induced membrane hyperpolarization. The involvement of specific Cl<jats:sup>\u2212<\/jats:sup> conductance was established with 9\u2010anthracene carboxylic acid (9\u2010AC). At 100 \u03bc<jats:sc>m<\/jats:sc>, 9\u2010AC reduced the loss of force due to hyperkalaemia, while at 200 \u03bc<jats:sc>m<\/jats:sc>, 9\u2010AC completely prevented loss of force. To study the role of the Na<jats:sup>+<\/jats:sup>\u2212K<jats:sup>+<\/jats:sup>\u22122Cl<jats:sup>\u2212<\/jats:sup> cotransporter (NKCC1) in this matter, we added 400 \u03bc<jats:sc>m<\/jats:sc> of the NKCC inhibitor bumetanide to the incubation medium. This did not affect the hyperkalaemia\u2010induced loss of force. We conclude that Cl<jats:sup>\u2212<\/jats:sup> exerts a permanent depolarizing influence on <jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub>. This influence of Cl<jats:sup>\u2212<\/jats:sup> on <jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub>, in combination with a large membrane conductance, can apparently have two different effects on hyperkalaemia\u2010induced loss of force. It might exert a stabilizing influence on force production during short periods of hyperkalaemia, but it can add to the loss of force during prolonged periods of hyperkalaemia.<\/jats:p>","DOI":"10.1113\/jphysiol.2004.071498","type":"journal-article","created":{"date-parts":[[2004,9,3]],"date-time":"2004-09-03T00:13:51Z","timestamp":1094170431000},"page":"169-181","source":"Crossref","is-referenced-by-count":16,"title":["Reducing chloride conductance prevents hyperkalaemia\u2010induced loss of twitch force in rat slow\u2010twitch muscle"],"prefix":"10.1113","volume":"561","author":[{"given":"Maarten Geert","family":"Van Emst","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sjoerd","family":"Klarenbeek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arend","family":"Schot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaap 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