title: Bumetanide prevents transient decreases in muscle force in murine hypokalemic periodic paralysis.
abstract: OBJECTIVE
  To test the hypothesis that inhibition of the Na-K-2Cl transporter with bumetanide will reduce the susceptibility to decreases in muscle force in a mouse model of hypokalemic periodic paralysis (HypoPP).
  
  
  METHODS
  In vitro contraction tests were performed on soleus muscle isolated from mice with knock-in missense mutations that result in HypoPP (sodium channel NaV1.4-R669H) or hyperkalemic periodic paralysis (HyperPP; sodium channel NaV1.4-M1592V).
  
  
  RESULTS
  Bumetanide prevented the development of weakness in 2 mM K(+) and also restored force during an established attack of HypoPP. Stimulation of the Na-K-2Cl transporter via induction of hyperosmolality exacerbated the weakness seen in low K(+) and was also prevented by bumetanide. Bumetanide was more efficacious than acetazolamide for preventing weakness in low K(+) conditions. Decreases in force in HyperPP muscle exposed to 10 mM K(+) were not prevented by treatment with bumetanide.
  
  
  CONCLUSIONS
  The Na-K-2Cl inhibitor bumetanide was highly effective in preventing attacks of weakness in the NaV1.4-R669H mouse model of HypoPP and should be considered for management of patients with HypoPP due to sodium channel mutations. Dehydration may aggravate HypoPP by stimulating the Na-K-2Cl transporter.
authors: Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, USA.
authors: Fenfen
authors: F
authors: Wu
authors: Wentao
authors: W
authors: Mi
authors: Stephen C
authors: SC
authors: Cannon
mesh_terms: D000818:Animals; D002034:Bumetanide / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D055879:Gene Knock-In Techniques; D020514:Hypokalemic Periodic Paralysis / Q000503:physiopathology* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D020125:Mutation, Missense / Q000502:physiology; D009924:Organ Culture Techniques
chemical_list: D002034:Bumetanide