Stimulation of NMDA receptors activates calpain in cultured hippocampal slices.
The hypothesis that intense stimulation of NMDA receptors activates calpain was tested in long-term cultures of hippocampus. Slices prepared from 10-day-old rats were maintained for periods of up to 6 weeks and then assayed for a stable breakdown product that results from the proteolysis of spectrin by calpain. The breakdown product increased dramatically during the first 24 h after tissue preparation and then decreased to a low level that remained unchanged for weeks. NMDA caused a 2- to 3-fold increase in breakdown product that rose linearly with time (5-30 min) and was blocked by the receptor antagonist MK-801. The effect of NMDA was the same throughout the culture period and was dependent upon the concentration of extracellular calcium with no effect at 2 mM and maximal effect at 4 mM calcium. These results indicate that rapid activation of calpain occurs in undamaged hippocampal neurons following stimulation of NMDA receptors.
del Cerro
S
S
Center for the Neurobiology of Learning and Memory, University of California, Irvine 92717-3800.
Arai
A
A
Kessler
M
M
Bahr
B A
BA
Vanderklish
P
P
Rivera
S
S
Lynch
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism*; D046508:Culture Techniques; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D009994:Osmolar Concentration; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013049:Spectrin / Q000378:metabolism; D013997:Time Factors
D016194:Receptors, N-Methyl-D-Aspartate; D013049:Spectrin; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D002154:Calpain; D002118:Calcium