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

Fenfen Wu, Wentao Mi, Stephen C. Cannon

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1110-1116
Number of pages7
JournalNeurology
Volume80
Issue number12
DOIs
StatePublished - Mar 19 2013

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Hypokalemic Periodic Paralysis
Bumetanide
Hyperkalemic Periodic Paralysis
Muscles
Sodium Channels
Acetazolamide
Missense Mutation
Dehydration
Skeletal Muscle
Mouse
Mutation

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Bumetanide prevents transient decreases in muscle force in murine hypokalemic periodic paralysis. / Wu, Fenfen; Mi, Wentao; Cannon, Stephen C.

In: Neurology, Vol. 80, No. 12, 19.03.2013, p. 1110-1116.

Research output: Contribution to journalArticle

Wu, Fenfen ; Mi, Wentao ; Cannon, Stephen C. / Bumetanide prevents transient decreases in muscle force in murine hypokalemic periodic paralysis. In: Neurology. 2013 ; Vol. 80, No. 12. pp. 1110-1116.
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