{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T15:26:50Z","timestamp":1765294010378},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,2,23]],"date-time":"2004-02-23T00:00:00Z","timestamp":1077494400000},"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":[[2004,3]]},"abstract":"<jats:p>This study investigated membrane transport mechanisms influencing relative changes in cell volume (<jats:italic>V<\/jats:italic>) and resting membrane potential (<jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub>) following osmotic challenge in amphibian skeletal muscle fibres. It demonstrated a stabilization of <jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub> despite cell shrinkage, which was attributable to elevation of intracellular [Cl<jats:sup>\u2212<\/jats:sup>] above electrochemical equilibrium through Na<jats:sup>+<\/jats:sup>\u2013Cl<jats:sup>\u2212<\/jats:sup> and Na<jats:sup>+<\/jats:sup>\u2212K<jats:sup>+<\/jats:sup>\u22122Cl<jats:sup>\u2212<\/jats:sup> cotransporter action following exposures to extracellular hypertonicity. Fibre volumes (<jats:italic>V<\/jats:italic>) determined by confocal microscope <jats:italic>xz\u2010<\/jats:italic>scanning of cutaneous pectoris muscle fibres varied linearly with [1\/extracellular osmolarity], showing insignificant volume corrections, in fibres studied in Cl<jats:sup>\u2212<\/jats:sup>\u2010free, normal and Na<jats:sup>+<\/jats:sup>\u2010free Ringer solutions and in the presence of bumetanide, chlorothiazide and ouabain. The observed volume changes following increases in extracellular tonicity were compared with microelectrode measurements of steady\u2010state resting potentials (<jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub>). Fibres in isotonic Cl<jats:sup>\u2212<\/jats:sup>\u2010free, normal and Na<jats:sup>+<\/jats:sup>\u2010free Ringer solutions showed similar <jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub> values consistent with previously reported permeability ratios <jats:italic>P<\/jats:italic><jats:sub>Na<\/jats:sub>\/<jats:italic>P<\/jats:italic><jats:sub>K<\/jats:sub><jats:italic>(<\/jats:italic>0.03\u20130.05) and <jats:italic>P<\/jats:italic><jats:sub>Cl<\/jats:sub>\/<jats:italic>P<\/jats:italic><jats:sub>K<\/jats:sub> (\u223c2.0) and intracellular [Na<jats:sup>+<\/jats:sup>], [K<jats:sup>+<\/jats:sup>] and [Cl<jats:sup>\u2212<\/jats:sup>]. Increased extracellular osmolarities produced hyperpolarizing shifts in <jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub> in fibres studied in Cl<jats:sup>\u2212<\/jats:sup>\u2010free Ringer solution consistent with the Goldman\u2010Hodgkin\u2010Katz (GHK) equation. In contrast, fibres exposed to hypertonic Ringer solutions of normal ionic composition showed no such <jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub> shifts, suggesting a Cl<jats:sup>\u2212<\/jats:sup>\u2010dependent stabilization of membrane potential. This stabilization of <jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub> was abolished by withdrawing extracellular Na<jats:sup>+<\/jats:sup> or by the combined presence of the Na<jats:sup>+<\/jats:sup>\u2013Cl<jats:sup>\u2212<\/jats:sup> cotransporter (NCC) inhibitor chlorothiazide (10 \u03bc<jats:sc>m<\/jats:sc>) and the Na<jats:sup>+<\/jats:sup>\u2212K<jats:sup>+<\/jats:sup>\u22122Cl<jats:sup>\u2212<\/jats:sup> cotransporter (NKCC) inhibitor bumetanide (10 \u03bc<jats:sc>m<\/jats:sc>), or the Na<jats:sup>+<\/jats:sup>\u2212K<jats:sup>+<\/jats:sup>\u2010ATPase inhibitor ouabain (1 or 10 \u03bc<jats:sc>m<\/jats:sc>) <jats:italic>during<\/jats:italic> alterations in extracellular osmolarity. Application of such agents <jats:italic>after<\/jats:italic> such increases in tonicity only produced a hyperpolarization after a time delay, as expected for passive Cl<jats:sup>\u2212<\/jats:sup> equilibration. These findings suggest a model that implicates the NCC and\/or NKCC in fluxes that maintain [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> above its electrochemical equilibrium. Such splinting of [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> in combination with the high <jats:italic>P<\/jats:italic><jats:sub>Cl<\/jats:sub>\/<jats:italic>P<\/jats:italic><jats:sub>K<\/jats:sub> of skeletal muscle stabilizes <jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub> despite volume changes produced by extracellular hypertonicity, but at the expense of a cellular capacity for regulatory volume increases (RVIs). In situations where <jats:italic>P<\/jats:italic><jats:sub>Cl<\/jats:sub>\/<jats:italic>P<\/jats:italic><jats:sub>K<\/jats:sub> is low, the same cotransporters would instead permit RVIs but at the expense of a capacity to stabilize <jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub>.<\/jats:p>","DOI":"10.1113\/jphysiol.2003.058545","type":"journal-article","created":{"date-parts":[[2003,12,30]],"date-time":"2003-12-30T01:13:08Z","timestamp":1072746788000},"page":"423-438","source":"Crossref","is-referenced-by-count":24,"title":["Membrane potential stabilization in amphibian skeletal muscle fibres in hypertonic solutions"],"prefix":"10.1113","volume":"555","author":[{"given":"Emily A.","family":"Ferenczi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James 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