{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T10:47:19Z","timestamp":1740134839436,"version":"3.37.3"},"reference-count":64,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T00:00:00Z","timestamp":1542672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Govermental funding for young scientist"},{"name":"DADD"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>During myotonia congenita, reduced chloride (Cl<jats:sup>\u2212<\/jats:sup>) conductance results in impaired muscle relaxation and increased muscle stiffness after forceful voluntary contraction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Repetitive contraction of myotonic muscle decreases or even abolishes myotonic muscle stiffness, a phenomenon called \u2018warm up\u2019.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Pharmacological inhibition of low Cl<jats:sup>\u2212<\/jats:sup> channels by anthracene\u20109\u2010carboxylic acid in muscle from mice and ADR (\u2018arrested development of righting response\u2019) muscle from mice showed a relaxation deficit under physiological conditions compared to wild\u2010type muscle.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>At increased osmolarity up to 400\u00a0mosmol\u00a0L<jats:sup>\u20131<\/jats:sup>, the relaxation deficit of myotonic muscle almost reached that of control muscle.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These effects were mediated by the cation and anion cotransporter, NKCC1, and anti\u2010myotonic effects of hypertonicity were at least partly antagonized by the application of bumetanide.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Low chloride\u2010conductance myotonia is caused by mutations in the skeletal muscle chloride (Cl<jats:sup>\u2212<\/jats:sup>) channel gene type 1 (CLCN1). Reduced Cl<jats:sup>\u2212<\/jats:sup> conductance of the mutated channels results in impaired muscle relaxation and increased muscle stiffness after forceful voluntary contraction. Exercise decreases muscle stiffness, a phenomena called \u2018warm up\u2019. To gain further insight into the patho\u2010mechanism of impaired muscle stiffness and the warm\u2010up phenomenon, we characterized the effects of increased osmolarity on myotonic function. Functional force and membrane potential measurements were performed on muscle specimens of ADR (\u2018arrested development of righting response\u2019) mice (an animal model for low gCl<jats:sup>\u2013<\/jats:sup> conductance myotonia) and pharmacologically\u2010induced myotonia. Specimens were exposed to solutions of increasing osmolarity at the same time as force and membrane potentials were monitored. In the second set of experiments, ADR muscle and pharmacologically\u2010induced myotonic muscle were exposed to an antagonist of NKCC1. Upon osmotic stress, ADR muscle was depolarized to a lesser extent than control wild\u2010type muscle. High osmolarity diminished myotonia and facilitated the warm\u2010up phenomenon as depicted by a faster muscle relaxation time (<jats:italic>T<\/jats:italic><jats:sub>90\/10<\/jats:sub>). Osmotic stress primarily resulted in the activation of the NKCC1. The inhibition of NKCC1 with bumetanide prevented the depolarization and reversed the anti\u2010myotonic effect of high osmolarity. Increased osmolarity decreased signs of myotonia and facilitated the warm\u2010up phenomenon in different <jats:italic>in vitro<\/jats:italic> models of myotonia. Activation of NKCC1 activity promotes warm\u2010up and reduces the number of contractions required to achieve normal relaxation kinetics.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp276528","type":"journal-article","created":{"date-parts":[[2018,10,5]],"date-time":"2018-10-05T19:37:09Z","timestamp":1538768229000},"page":"225-235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Elevation of extracellular osmolarity improves signs of myotonia congenita <i>in vitro<\/i>: a preclinical animal study"],"prefix":"10.1113","volume":"597","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5789-7926","authenticated-orcid":false,"given":"Kerstin","family":"Hoppe","sequence":"first","affiliation":[{"name":"Department of Anaesthesia Critical Care Medicine and Pain Therapy University of Frankfurt  Frankfurt 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