RESUMO
This review is devoted to the action of amyloid-beta peptide on the functional activity of intracellular and plasmalemmal calcium-regulated structures in cultured hyppocampal neurons: mitochondria and voltage-gated calcium channels. A comparative analysis of relative changes of plasmalemmal structures in such neurodegenerative diseases as Alzheimer's illness and diabetic neuropathy has been made.
Assuntos
Doença de Alzheimer/etiologia , Sinalização do Cálcio , Neuropatias Diabéticas/etiologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/farmacologia , Animais , Canais de Cálcio/metabolismo , Sinalização do Cálcio/fisiologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Neuropatias Diabéticas/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , RatosRESUMO
Anomalous accumulation of beta-amyloid peptide in cerebral neurons plays central role in pathogenesis of Alzheimer's disease (AD). One of the essential pathogenetic factors at AD is disturbance of calcium homeostasis in neurons of central nervous system. It was determined in this work that 24-hour incubation of hippocampal cell culture with beta-amyloid peptide caused more than twofold elevation of basal calcium concentration relatively to control value (153.4 +/- 11.5 and 71.7 +/- 5.4 nM respectively; P < 0.05, n=7). Using whole cell patch-clamp technique it was detected that calcium current density in beta-amyloid-treated cells was 70% higher (P < 0.05, n=12) than in control ones. Obtained data broaden our comprehension of disturbance of molecular mechanisms of calcium homeostasis in neurons in AD, particularly mechanisms of elevation of basal calcium concentration by means of enhancement of calcium influx through plasmalemmal voltage-gated calcium channels.
