title: Streptomycin reduces stretch-induced membrane permeability in muscles from mdx mice.
abstract: It is well-known that muscles from mdx mice are more susceptible to membrane damage from eccentric contractions than wild-type muscles. The present study tested the hypothesis that the stretch-induced membrane permeability in dystrophic muscle is due to Ca(2+) entry through stretch-activated channels (SACs) and the subsequent activation of Ca(2+) -dependent degradative pathways. Eccentric contractions were carried out on muscles from mdx and wild-type mice, both on isolated muscles and on intact mice subjected to downhill running on a treadmill. In isolated muscles the SAC blockers, streptomycin and GsMTx4, improved force and significantly reduced the uptake of procion orange dye into fibres from mdx muscles, which increased progressively over 60 min after the eccentric contractions. In experiments on intact mdx mice, streptomycin also partially prevented the reduced force and the increased membrane permeability (Evans Blue Dye uptake). The results suggest that Ca(2+) entry through SACs activates Ca(2+) -dependent pathways, which are the main cause of the increased membrane permeability in mdx muscle.
authors.affiliation: School of Medical Sciences and Institute for Biomedical Research, University of Sydney F13, Sydney, NSW, Australia.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Whitehead
authors.forename: Margaret
authors.initials: M
authors.lastname: Streamer
authors.forename: Lynn I
authors.initials: LI
authors.lastname: Lusambili
authors.forename: Frederick
authors.initials: F
authors.lastname: Sachs
authors.forename: David G
authors.initials: DG
authors.lastname: Allen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D004396:Coloring Agents; D004195:Disease Models, Animal; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism / Q000503:physiopathology; D010455:Peptides / Q000494:pharmacology; D010805:Physical Conditioning, Animal / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D013111:Spider Venoms / Q000494:pharmacology; D013307:Streptomycin / Q000494:pharmacology
chemical_list: D004396:Coloring Agents; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; C411249:MTx4 protein, Grammostola spatulata; D009124:Muscle Proteins; D010455:Peptides; D026902:Potassium Channel Blockers; D013111:Spider Venoms; D002118:Calcium; D013307:Streptomycin