Inhibitory effect of ferrous ions on increase in intracellular Ca2+ induced by activation of the NMDA receptor channels

• Published in: Japanese Journal of Pharmacology 2001, Vol.85 (suppl.1), p.148-148
• Main Authors: Noritaka Nakamichi, Hiroshi Ohno, Nobuyuki Kuramoto, Masako Takayanagi, Yoichi Nakamura, Yukio Yoneda
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

An elevation of intracellular free Ca ions is supposed to he a key trigger for intracellular signaling cascade of a transient extracellular signal by L-glutamic acid to the nucleus through activation of the NMDA receptor channels on synaptic membranes. This research was aimed at elucidation of mechanisms underlying these intracellular processes for NMDA signaling in neurons. Rat cortical cultures for 3 DIV were preincubated with fluo-3 AM and then subjected to fluorescence image analysis using a confocal microscope. An increase in the fluorescence was observed in both cell bodies and neurites 200 msec after the addition of NMDA and sustained during the exposure to NMDA at least for 30 min. The addition of KCl also induced a marked increase in the fluorescence with a rapid onset of decline within 2 min even in the persistent presence of KCl. The addition of FeCl_2 prominently reduced the fluorescence increased by NMDA in a concentration-dependent manner at a concentration range of 10 to 200 μM, without markedly affecting that by KCl when added 6 min after the addition of either stimulant. These results suggest that ferrous ions may prevent Ca influx across the membrane through the NMDA receptor channels, but not through the voltage-gated Ca^2+ channels, in cultured rat cortical neurons.