15 - Effects of Amyotrophic Lateral Sclerosis IgGs on Calcium Homeostasis in Neural Cells

Abstract

This chapter presents a non-invasive study of the effects of amyotrophic lateral sclerosis immunoglobulins (IgGs) on calcium homeostasis in neural cells. The study was performed by using confocal laser scanning microscopy and rat hippocampal pyramidal neurons in culture were employed as a convenient model of identified central neurons endowed with various classes of calcium ion channel. Hippocampal cell cultures were prepared from 2–4 day old rats, and pyramidal neurons after 5–15 days in culture were preincubated in standard experimental solution supplemented with 0.5% BSA and 0.05% Pluronic-F127. Potassium chloride-induced transient [Ca2+]i rise was partially blocked by cadmium and was completely abolished in a calcium-free medium. In the presence of an inhibitor of ionotropic glutamate receptors (CNQX or kynurenic acid), the potassium chloride-induced response was affected by specific blockers of L-, N-, or P/Q-type voltage-gated calcium ion channels, each suppressing the [Ca2+]i transient by about 30–40%. In the presence of CNQX or kynurenic acid, ALS IgGs evoked a depression of the potassium-induced response, which did not occur with IgGs from healthy donors.