{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:30:19Z","timestamp":1778275819570,"version":"3.51.4"},"reference-count":46,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2010,7,16]],"date-time":"2010-07-16T00:00:00Z","timestamp":1279238400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2010,7,15]]},"abstract":"<jats:p>It has been shown that the voltage (<jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub>) dependence of ClC Cl<jats:sup>\u2212<\/jats:sup> channels is conferred by interaction of the protopore gate with H<jats:sup>+<\/jats:sup> ions. However, in this paper we present evidence which indicates that permeant Cl<jats:sup>\u2212<\/jats:sup> ions contribute to <jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub>\u2010dependent gating of the broadly distributed ClC\u20102 Cl<jats:sup>\u2212<\/jats:sup> channel. The apparent open probability (<jats:italic>P<\/jats:italic><jats:sub>A<\/jats:sub>) of ClC\u20102 was enhanced either by changing the [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> from 10 to 200 m<jats:sc>m<\/jats:sc> or by keeping the [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> low (10 m<jats:sc>m<\/jats:sc>) and then raising [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>o<\/jats:sub> from 10 to 140 m<jats:sc>m<\/jats:sc>. Additionally, these changes in [Cl<jats:sup>\u2212<\/jats:sup>] slowed down channel closing at positive <jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub> suggesting that high [Cl<jats:sup>\u2212<\/jats:sup>] increased pore occupancy thus hindering closing of the protopore gate. The identity of the permeant anion was also important since the <jats:italic>P<\/jats:italic><jats:sub>A<\/jats:sub>(<jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub>) curves were nearly identical with Cl<jats:sup>\u2212<\/jats:sup> or Br<jats:sup>\u2212<\/jats:sup> but shifted to negative voltages in the presence of SCN<jats:sup>\u2212<\/jats:sup> ions. In addition, gating, closing rate and reversal potential displayed anomalous mole fraction behaviour in a SCN<jats:sup>\u2212<\/jats:sup>\/Cl<jats:sup>\u2212<\/jats:sup> mixture in agreement with the idea that pore occupancy by different permeant anions modifies the <jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub> dependence ClC\u20102 gating. Based on the ec1\u2010ClC anion pathway, we hypothesized that opening of the protopore gate is facilitated when Cl<jats:sup>\u2212<\/jats:sup> ions dwell in the central binding site. In contrast, when Cl<jats:sup>\u2212<\/jats:sup> ions dwell in the external binding site they prevent the gate from closing. Finally, this Cl<jats:sup>\u2212<\/jats:sup>\u2010dependent gating in ClC\u20102 channels is of physiological relevance since an increase in [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>o<\/jats:sub> enhances channel opening when the [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> is in the physiological range.<\/jats:p>","DOI":"10.1113\/jphysiol.2010.189175","type":"journal-article","created":{"date-parts":[[2010,5,25]],"date-time":"2010-05-25T03:39:43Z","timestamp":1274758783000},"page":"2545-2556","source":"Crossref","is-referenced-by-count":26,"title":["Permeant anions contribute to voltage dependence of ClC\u20102 chloride channel by interacting with the protopore gate"],"prefix":"10.1113","volume":"588","author":[{"given":"Jorge E.","family":"S\u00e1nchez\u2010Rodr\u00edguez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 A.","family":"De 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