title: Voltage-gated sodium channel (SkM1) content in dystrophin-deficient muscle.
abstract: The membrane cytoskeleton is increasingly considered as both an anchor and a functional modulator for ion channels. The cytoskeletal disruptions that occur in the absence of dystrophin led us to investigate the voltage-gated sodium channel (SkM1) content in the extensor digitorum longus (EDL) muscle of the dystrophin-deficient mdx mouse. Levels of SkM1 mRNA were determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). A C-terminal portion of the mouse-specific SkM1 alpha-subunit cDNA (mScn4a) was identified first. SkM1 mRNA levels were as abundant in mdx as in normal muscle, thus suggesting that the transcriptional rate of SkM1 remains unchanged in mdx muscle. However, SkMI density in the extrajunctional sarcolemma was shown to be significantly reduced in mdx muscle, using confocal immunofluorescence image analysis. This decrease was found to be associated with a reduction in the number of SkM1-rich fast-twitch IIb fibres in mdx muscle. In addition, lowered SkM1 sarcolemmal labelling was found in all mdx fibres regardless of their metabolic type. These results suggest the existence of a perturbation of SkM1 anchorage to the plasma membrane. Such an alteration is likely to be related to the 50% decrease in mdx muscle of the dystrophin-associated syntrophins, which are presumed to be involved in SkM1 anchorage. However, the moderate reduction in SkM1 density (-12.7%) observed in mdx muscle argues in favour of a non-exclusive role of syntrophins in SkM1 anchorage and suggests that other membrane-associated proteins are probably also involved.
authors.affiliation: Université Claude Bernard Lyon 1, Laboratoire de Physiologie des Eléments Excitables, Villeurbanne, France.
authors.forename: P
authors.initials: P
authors.lastname: Ribaux
authors.forename: F
authors.initials: F
authors.lastname: Bleicher
authors.forename: M L
authors.initials: ML
authors.lastname: Couble
authors.forename: J
authors.initials: J
authors.lastname: Amsellem
authors.forename: S A
authors.initials: SA
authors.lastname: Cohen
authors.forename: C
authors.initials: C
authors.lastname: Berthier
authors.forename: S
authors.initials: S
authors.lastname: Blaineau
mesh_terms: D000818:Animals; D001483:Base Sequence; D016384:Consensus Sequence; D016189:Dystrophin / Q000235:genetics*; D015870:Gene Expression; D007150:Immunohistochemistry; D015640:Ion Channel Gating / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008969:Molecular Sequence Data; D018656:Muscle Fibers, Fast-Twitch / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D018657:Muscle Fibers, Slow-Twitch / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012508:Sarcolemma / Q000737:chemistry / Q000378:metabolism; D015222:Sodium Channels / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016189:Dystrophin; D012333:RNA, Messenger; D015222:Sodium Channels