Nitric oxide modulates calcium entry through P/Q-type calcium channels and N-methyl-d-aspartate receptors in rat cortical neurons

Voltage-gated calcium channels (VGCC) and N-methyl-d-aspartate receptors (NMDAR) account for most of the depolarization-induced neuronal calcium entry. The susceptibility of individual routes of calcium entry for nitric oxide (NO) is largely unknown. We loaded cultured rat cortical neurons with fluo-4 acetoxymethylester to study the effect of the NO synthase inhibitor Nω-nitro-l-arginine and the NO donor S-nitroso-N-acetylpenicillamine on the intracellular calcium concentration ([Ca²⁺]_i). The potassium-induced [Ca²⁺]_i increase was amplified by Nω-nitro-l-arginine and attenuated by S-nitroso-N-acetylpenicillamine. This modulation was abolished by either the P/Q-type VGCC antagonist ω-agatoxin IVA or by the NMDAR antagonist MK-801, but not by N-type (ω-conotoxin GVIA) or L-type (nimodipine) VGCC blockers. These results suggest that NO can modulate neuronal calcium entry during depolarization by interacting with P/Q-type VGCC and NMDAR.