title: [Ionic and molecular mechanisms of beta-amyloid-induced depolarization of the mouse skeletal muscle fibres].
abstract: Excess production and accumulation of beta-amyloid peptide (betaAP) are central for pathogenesis of Alzheimer's disease. Numerous studies showed that betaAP possessed wide range of toxic effects on neurons, however the mechanism of betaAP influence on another types of excitable cells, for example, skeletal muscle fibres, is unknown. In electrophysiological experiments on the mouse diaphragm, we found for the first time that betaAP (25-35 fragment, 10-6 M) disturbs the processes of the resting membrane potential generation in muscle fibres, leading to depolarization by two mechanisms: 1) inhibition of Na+,K(+)-ATPase, which leads to loss of impact of this pump to the resting membrane potential; 2) increase of membrane cationic permeability due to formation of "amyloid" channels blocked with Zn2+ ions. Our results significantly broaden current understanding of mechanisms of motor disturbances and skeletal muscle pathology in Alzheimer's disease, inclusion body myositis and other betaAP-related disorders.
authors.forename: M A
authors.initials: MA
authors.lastname: Mukhamediarov
authors.forename: E M
authors.initials: EM
authors.lastname: Volkov
authors.forename: A V
authors.initials: AV
authors.lastname: Leushina
authors.forename: Iu O
authors.initials: IuO
authors.lastname: Kochunova
authors.forename: A
authors.initials: A
authors.lastname: Palotas
authors.forename: A L
authors.initials: AL
authors.lastname: Zefirov
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D003964:Diaphragm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015194:Diffusion Chambers, Culture; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008839:Microelectrodes; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018979:Myositis, Inclusion Body / Q000473:pathology / Q000503:physiopathology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D046509:Tissue Culture Techniques / Q000379:methods*; D015032:Zinc / Q000009:adverse effects / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D011994:Recombinant Proteins; C439320:amyloid beta-protein (25-36); D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D015032:Zinc