β-Amyloid-Induced Changes in Calcium Homeostasis in Cultured Hippocampal Neurons of the Rat

A two-wave technique of calciometry with the use of a fluorescence dye, fura-2/AM, was applied for examination of the effect of a protein, beta-amyloid (the main component of senile plaques in Alzheimer's disease), on calcium homeostasis in cultured neurons of the rat hippocampus; beta-amyloid was added to the culture medium. In most neurons, the effect of beta-amyloid appeared as a more than twofold increase in the basic calcium concentration, as compared with the control (153.4 +/- 11.5 and 71.7 +/- 5.4 nM, respectively; P < 0.05). The characteristics of calcium transients induced by application of hyperpotassium solution also changed; the amplitude of these transients decreased, and the duration of a part corresponding to calcium release from the cell (rundown of the transient) increased. The mean amplitude of calcium transients under control conditions was 447.5 +/- 20.1 nM, while after incubation in the presence of beta-amyloid this index dropped to 278.4 +/- 22.6 nM. Under control conditions, the decline phase of calcium transients lasted, on average, 100 +/- 6 sec, while after incubation of hippocampal cell cultures in the presence of beta-amyloid this phase lasted 250 +/- 10 sec. Therefore, an excess of beta-amyloid influences significantly calcium homeostasis in the nerve cells by disturbing functions of the calcium-controlling systems, such as voltage-operated calcium channels of the plasma membrane and calcium stores of the mitochondria and endoplasmic reticulum.