Bumetanide prevents transient decreases in muscle force in murine hypokalemic periodic paralysis

Neurology. 2013 Mar 19;80(12):1110-6. doi: 10.1212/WNL.0b013e3182886a0e. Epub 2013 Feb 20.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bumetanide / pharmacology
  • Bumetanide / therapeutic use*
  • Female
  • Gene Knock-In Techniques
  • Hypokalemic Periodic Paralysis / physiopathology*
  • Hypokalemic Periodic Paralysis / prevention & control*
  • Male
  • Mice
  • Mice, Transgenic
  • Muscle Contraction / drug effects*
  • Muscle Contraction / physiology*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiology
  • Mutation, Missense / physiology
  • Organ Culture Techniques


  • Bumetanide