Stimulation of NMDA receptors activates calpain in cultured hippocampal slices

S del Cerro, A Arai, M Kessler, BA Bahr… - Neuroscience …, 1994 - Elsevier
S del Cerro, A Arai, M Kessler, BA Bahr, P Vanderklish, S Rivera, G Lynch
Neuroscience letters, 1994Elsevier
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 …
Abstract
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.
Elsevier