This review is focused on the composition and organization of the junctional subsarcolemmal cytoskeleton of adult muscle fibers. The cytoskeleton of muscle fibers is organized in functionally distinct compartments and the subsarcolemmal cytoskeleton itself can be broadly divided into junctional (myotendinous junction, neuromuscular junction and costameres) and non-junctional domains. In junctional zones three different multimolecular cytoskeletal complexes coexist: the focal adhesion-type, the spectrin-based and the dystrophin vs utrophin-based membrane skeleton systems. These complexes extend over several levels, from intracytoplasmic to subsarcolemmal and transmembranous; their common feature is the anchorage of actin filaments emanating from the intracytoplasmic level. The different cytoskeletal proteins, their putative roles and their interactions with various signaling pathways are presented here in detail. The subsarcolemmal cytoskeleton complexes are thought to play distinct physiological roles (membrane stabilization, force transmission to extracellular matrix, ionic channel anchorage, etc) but their colocalization on the three sarcolemmal junctional domains strongly suggests interrelated or common functions.

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Effects of chronic high-altitude hypoxia on the remodeling of right ventricle were examined in three age groups of rats: 2, 6, and 18 mo. The extent of right ventricular (RV) hypertrophy (RVH) showed an age-associated diminution. RV cell size and pericellular fibrosis showed a significant increase in the 2- and 6-mo-old exposed rats but not in the 18-mo-old exposed rats compared with control. A hyperplasic response was underscored in the three exposed age groups but appeared less pronounced in the 18-mo-old rats. A significant decrease in the transient outward potassium current (Ito) density was observed in RV cell only in the 2-mo-old exposed group compared with the control group. In the control group, there was a clear tendency for Ito density to decrease as a function of age. The sustained outward current density was modified neither by the hypoxia condition nor by the age. Neither the cytochrome c oxidase activity nor the heat shock protein 72 content in the RV was altered after hypoxic exposure regardless of age. The norepinephrine content in the RV was significantly decreased in each age group exposed to hypoxia when compared with their age-matched control group. Our findings indicate that the remodeling (at morphological and electrophysiological levels) induced by chronic hypoxia in the RV can be decreased by the natural aging process.

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.