Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

A calcium channel mutant mouse model of hypokalemic periodic paralysis.

Hypokalemic periodic paralysis (HypoPP) is a familial skeletal muscle disorder that presents with recurrent episodes of severe weakness lasting hours to days associated with reduced serum potassium (K+). HypoPP is genetically heterogeneous, with missense mutations of a calcium channel (Ca(V)1.1) or a sodium channel (Na(V)1.4) accounting for 60% and 20% of cases, respectively. The mechanistic link between Ca(V)1.1 mutations and the ictal loss of muscle excitability during an attack of weakness in HypoPP is unknown. To address this question, we developed a mouse model for HypoPP with a targeted Ca(V)1.1 R528H mutation. The Ca(V)1.1 R528H mice had a HypoPP phenotype for which low K+ challenge produced a paradoxical depolarization of the resting potential, loss of muscle excitability, and weakness. A vacuolar myopathy with dilated transverse tubules and disruption of the triad junctions impaired Ca2+ release and likely contributed to the mild permanent weakness. Fibers from the Ca(V)1.1 R528H mouse had a small anomalous inward current at the resting potential, similar to our observations in the Na(V)1.4 R669H HypoPP mouse model. This "gating pore current" may be a common mechanism for paradoxical depolarization and susceptibility to HypoPP arising from missense mutations in the S4 voltage sensor of either calcium or sodium channels.

Pubmed ID: 23187123 RIS Download

Mesh terms: Action Potentials | Analysis of Variance | Animals | Calcium Channels, L-Type | Disease Models, Animal | Electric Stimulation | Excitation Contraction Coupling | Female | Glucose | Humans | Hypokalemic Periodic Paralysis | In Vitro Techniques | Insulin | Lysosomal Storage Diseases | Male | Mice | Mice, 129 Strain | Muscle Contraction | Muscle Fibers, Skeletal | Muscle Weakness | Muscle, Skeletal | Muscular Diseases | Mutation, Missense | Phenotype

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIAMS NIH HHS, Id: R01 AR063182
  • Agency: NIAMS NIH HHS, Id: R01 AR042703
  • Agency: NIAMS NIH HHS, Id: R37 AR055099
  • Agency: NIAMS NIH HHS, Id: AR-063182
  • Agency: NIAMS NIH HHS, Id: AR-055099
  • Agency: NIAMS NIH HHS, Id: R01 AR055099
  • Agency: NIAMS NIH HHS, Id: AR-42703
  • Agency: NIAMS NIH HHS, Id: R37 AR042703

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.