Alzheimer's beta-amyloid-induced depolarization of skeletal muscle fibers: implications for motor dysfunctions in dementia.
Numerous findings obtained over the last decades suggest that accumulation of beta-amyloid peptide (betaAP) plays the central role in the pathogenesis of Alzheimer's disease. It is well established that betaAP has wide range of toxic effects on neurons in vitro and in vivo, however the influence of betaAP in the periphery and on various other types of excitable tissues, eg. skeletal muscle cells, is almost unknown despite the many non-cognitive and other extra-neuronal symptoms associated with Alzheimer's dementia. Here we utilized conventional electrophysiological technique to investigate the effects and mechanisms of betaAP action on the resting membrane potential of frog skeletal muscle fibers. betaAP in the range of concentrations from 10(-6) to 10(-8)M produced slow, significant, reversible depolarization of muscle fiber membranes. The impact developed and was washed out faster at higher concentrations of betaAP (10(-6)-0(-7)M). The effect of betaAP was completely absent when applied in Na+-free Tris+ solutions. betaAP-mediated depolarization was also prevented by tetrodotoxin (10(-5)M) pre-treatment and rescued by tetrodotoxin after-treatment. These findings suggest that betaAP-induced depolarization of skeletal muscle plasma membranes can significantly disturb the functioning of skeletal muscles and therefore contribute to motor dysfunction observed in Alzheimer's disease and other disorders associated with betaAP accumulation.
Mukhamedyarov
Marat A
MA
Department of Physiology, Kazan State Medical University, Kazan, Russia.
Grishin
Sergey N
SN
Yusupova
Elvina R
ER
Zefirov
Andrey L
AL
Palotás
András
A
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001001:Anura; D003704:Dementia / Q000378:metabolism*; D004594:Electrophysiology / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D013779:Tetrodotoxin