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Blockade by ferrous iron of Ca 2+ influx through N ‐methyl‐ d ‐aspartate receptor channels in immature cultured rat cortical neurons
Author(s) -
Nakamichi Noritaka,
Ohno Hiroshi,
Nakamura Yoichi,
Hirai Takao,
Kuramoto Nobuyuki,
Yoneda Yukio
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01042.x
Subject(s) - nmda receptor , ferrous , biophysics , cortical neurons , calcium , intracellular , chemistry , channel blocker , receptor , fluorescence , fluorescence microscope , in vitro , biochemistry , biology , microbiology and biotechnology , physics , organic chemistry , quantum mechanics
Rat cortical neurons cultured for 3 days in vitro were loaded with the fluorescent indicator fluo‐3 for assessment of intracellular free calcium ion (Ca 2+ ) concentrations with the aid of a confocal laser‐scanning microscope. In the absence of added MgCl 2 , the addition of NMDA induced a rapid but sustained increase in the number of fluorescent neurons in a concentration‐dependent manner at a concentration range of 1–100 µ m with the increase by KCl being transient. The addition of FeCl 2 , but not FeCl 3 , markedly inhibited the increase by NMDA in a reversible manner at concentrations of 10–200 µ m , without affecting that by KCl. Extensive analyses revealed clear differentiation between inhibitions by ferrous iron and other channel blockers known to date. The inhibition by FeCl 2 was completely prevented by the addition of two different iron chelators. Exposure to NMDA alone did not lead to cell death in immature cultured neurons, however, while further addition of FeCl 2 invariably induced neuronal cell death 24 h after exposure. These results give support to our previous proposal that NMDA receptor complex may contain a novel site sensitive to blockade by ferrous iron in rat brain.