N-methylaspartate-activated calcium channels in rat brain cortex slices. Effect of calcium channel blockers and of inhibitory and depressant substances.
N-Methyl-DL-aspartate, L-glutamate, kainate and DL-homocysteate were found to increase the initial rate and the maximal uptake of 45Ca into the non-inulin space of rat brain cortex slices incubated in vitro. The N-methylaspartate-stimulated calcium uptake was blocked by cadmium and cobalt ions, but not by the organic calcium channel blocker nifedipine or by tetrodotoxin, both of which stimulated the N-methylaspartate-independent calcium influx. gamma-Aminobutyrate increased the spontaneous calcium influx, and also reduced that stimulated by N-methylaspartate to the same level, as found with gamma-aminobutyrate alone. Adenosine (1-100 microM), ethanol (0.1 M), pentobarbital (10-100 microM) and morphine (0.2 mM), were unable to inhibit the N-methylaspartate-activated calcium influx. Ethanol (0.1 M), had no effect on the glutamate- or kainate-activated calcium influx. These findings suggest that the excitatory amino acids, because of their neuronal depolarizing action in brain cortex, lead to the opening of voltage-sensitive calcium channels, which may be blocked by cadmium, but not by the organic calcium channel antagonist, nifedipine. The activation of calcium channels by the excitatory amino acid N-methylaspartate, was entirely unaffected by the depressants ethanol, pentobarbital or morphine, or by the endogenous inhibitory substance, adenosine, thus suggesting that their inhibitory or depressant effects occur through interference with a neuronal mechanism unrelated to the one studied here. gamma-Aminobutyrate, on the other hand, considerably inhibited N-methylaspartate-induced calcium uptake, an effect interpreted as due to a gamma-aminobutyrate-induced increase in chloride conductance, that "clamps" the membrane potential and does not allow further depolarization by N-methylaspartate.
Riveros
N
N
Orrego
F
F
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003035:Cobalt / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology; D016202:N-Methylaspartate; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002492:Central Nervous System Depressants; D007473:Ion Channels; D002104:Cadmium; D001224:Aspartic Acid; D003035:Cobalt; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D009020:Morphine; D009543:Nifedipine