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 Nomega-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 Nomega-nitro-l-arginine and attenuated by S-nitroso-N-acetylpenicillamine. This modulation was abolished by either the P/Q-type VGCC antagonist omega-agatoxin IVA or by the NMDAR antagonist MK-801, but not by N-type (omega-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.
Petzold
Gabor C
GC
Department of Experimental Neurology, Charité-University Medicine Berlin, Schumannstr. 20-21, 10117 Berlin, Germany. gpetzold@mcb.harvard.edu
Scheibe
Franziska
F
Braun
Johann S
JS
Freyer
Dorette
D
Priller
Josef
J
Dirnagl
Ulrich
U
Dreier
Jens P
JP
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020865:Calcium Channels, P-Type / Q000378:metabolism*; D020907:Calcium Channels, Q-Type / Q000378:metabolism*; D002478:Cells, Cultured; D045604:Extracellular Fluid / Q000502:physiology; D007424:Intracellular Fluid / Q000378:metabolism; D019579:Neocortex / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D002118:Calcium