Lead-induced ER calcium release and inhibitory effects of methionine choline in cultured rat hippocampal neurons

Abstract

Lead, a ubiquitous neurotoxicant, can result in learning and memory dysfunction. Long term potentiation in the hippocampus, a potential neural substrate for learning and memory, is thought to be linked to calcium-triggered intracellular events. In this study, laser scanning confocal microscopy was used to examine the effects of Pb2+ on intracellular and endoplasmic reticulum free calcium concentration ([Ca2+]i and [Ca2+]ER) in cultured neonatal rat hippocampal neurons and their possible antagonism by methionine choline; understanding these effects would help explain the lead-induced cognitive and learning dysfunction and explore efficient safety and relief strategies. The results showed that Pb2+ increased [Ca2+]i and decreased [Ca2+]ER linearly in a time- and concentration-dependant manner, and Pb2+ addition after the applying of a ryanodine receptor (RyR) antagonist and an inositol-1,4,5-triphosphate receptor (IP3R) antagonist did not increase [Ca2+]i. The addition of 10, 20, or 40mmol/L methionine choline simultaneously with addition of 10μmol/L Pb2+ decreased [Ca2+]i in Ca2+-free culture medium by 39.0%, 66.0%, and 61.6%, respectively, in a concentration-dependant manner in a certain dose range. Our results suggest that Pb2+ induces ER calcium release to increase the resting [Ca2+]i; and methionine choline inhibit this increase in [Ca2+]i.