title: Reduced muscle-fiber conduction but normal slowing after cold exposure in paramyotonia congenita.
abstract: In this study we investigated a family with paramyotonia (PC) congenita caused by a Gly1306Val mutation in the voltage-gated sodium-channel gene SCN4A. A previous study showed that exposure to cold aggravates the muscle stiffness in patients with this mutation. However, the mechanism behind cold sensitivity and the sodium-channel defect remained unclear. In order to gain a better understanding of sarcolemmal propagation in these patients, we measured muscle-fiber conduction velocity (MFCV) invasively. We studied four PC patients and four healthy subjects at room temperature. After the muscle was cooled, MFCV was measured again in the two PC patients and four control subjects. MFCV was significantly lower in the PC patients at room temperature, compatible with dysfunctional sodium channels. After cooling, MFCV was significantly lower in both groups as compared with room temperature. The relative slowing was 1.4% per degrees C for PC patients and 1.5% per degrees C for healthy subjects. These results indicate that, in these PC patients, mutant and wild-type sodium channels respond equally to cold exposure. Thus, MFCV is abnormal in these patients, but the aggravation of muscle stiffness cannot be explained by an abnormal sarcolemmal response to cold.
authors.affiliation: Department of Clinical Neurophysiology, Institute of Neurology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Blijham
authors.forename: Gea
authors.initials: G
authors.lastname: Drost
authors.forename: Dick F
authors.initials: DF
authors.lastname: Stegeman
authors.forename: Machiel J
authors.initials: MJ
authors.lastname: Zwarts
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000328:Adult; D003080:Cold Temperature / Q000009:adverse effects; D004576:Electromyography; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics; D020967:Myotonic Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D062553:NAV1.4 Voltage-Gated Sodium Channel; D011930:Reaction Time / Q000235:genetics; D012508:Sarcolemma / Q000235:genetics / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics*; D013997:Time Factors