Abstract | OBJECTIVE: Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials ( myotonia), producing muscle stiffness. In patients, muscle stiffness lessens with exercise, a change known as the warmup phenomenon. Our goal was to identify the mechanism underlying warmup and to use this information to guide development of novel therapy. METHODS: To determine the mechanism underlying warmup, we used a recently discovered drug to eliminate muscle contraction, thus allowing prolonged intracellular recording from individual muscle fibers during induction of warmup in a mouse model of myotonia congenita. RESULTS: INTERPRETATION:
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Authors | Kevin R Novak, Jennifer Norman, Jacob R Mitchell, Martin J Pinter, Mark M Rich |
Journal | Annals of neurology
(Ann Neurol)
Vol. 77
Issue 2
Pg. 320-32
(Feb 2015)
ISSN: 1531-8249 [Electronic] United States |
PMID | 25515836
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | © 2014 American Neurological Association. |
Chemical References |
- Acetanilides
- CLC-1 channel
- Chloride Channels
- Piperazines
- Sodium Channel Blockers
- Ranolazine
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Topics |
- Acetanilides
(administration & dosage)
- Animals
- Chloride Channels
(antagonists & inhibitors, physiology)
- Drug Delivery Systems
(methods)
- Mice
- Mice, Transgenic
- Muscle Contraction
(drug effects, physiology)
- Myotonia Congenita
(drug therapy, genetics, physiopathology)
- Organ Culture Techniques
- Piperazines
(administration & dosage)
- Ranolazine
- Sodium Channel Blockers
(administration & dosage)
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