TY - JOUR
T1 - Carbachol can potentiate N-methyl-d-aspartate responses in the rat hippocampus by a staurosporine and thapsigargin-insensitive mechanism
AU - Harvey, Jenni
AU - Balasubramaniam, Richard
AU - Collingridge, Graham L.
PY - 1993/11/12
Y1 - 1993/11/12
N2 - Experiments were performed to investigate the mechanism underlying the potentiation of N-methyl-d-aspartate (NMDA) responses by carbachol (CCh) in the CA1 region of rat hippocampal slices. CCh (300 nM) potentiated responses to NMDA, but not to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), in a readily reversible manner. Potentiation occurred in slices treated with 200 nM tetrodotoxin and perfused with Mg2+-free medium. It also occurred in slices treated with either staurosporine (1 μM), which is a potent inhibitor of a variety of protein kinases including protein kinase C (PKC), or thapsigargin (10 μM), which depletes intracellular Ca2+ stores by preventing their refilling. However, CCh-induced potentiation was abolished in slices perfused with Ca2+-free medium. These data suggest that low concentrations of CCh can acutely potentiate NMDA responses in the hippocampus by a Ca2+-sensitive process that is probably independent of both the activation of PKC and the release of Ca2+ from intracellular stores. This mechanism is similar to that underlying the potentiation of NMDA responses by the metabotropic glutamate receptor (mGluR) agonist. aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD).
AB - Experiments were performed to investigate the mechanism underlying the potentiation of N-methyl-d-aspartate (NMDA) responses by carbachol (CCh) in the CA1 region of rat hippocampal slices. CCh (300 nM) potentiated responses to NMDA, but not to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), in a readily reversible manner. Potentiation occurred in slices treated with 200 nM tetrodotoxin and perfused with Mg2+-free medium. It also occurred in slices treated with either staurosporine (1 μM), which is a potent inhibitor of a variety of protein kinases including protein kinase C (PKC), or thapsigargin (10 μM), which depletes intracellular Ca2+ stores by preventing their refilling. However, CCh-induced potentiation was abolished in slices perfused with Ca2+-free medium. These data suggest that low concentrations of CCh can acutely potentiate NMDA responses in the hippocampus by a Ca2+-sensitive process that is probably independent of both the activation of PKC and the release of Ca2+ from intracellular stores. This mechanism is similar to that underlying the potentiation of NMDA responses by the metabotropic glutamate receptor (mGluR) agonist. aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD).
KW - Ca
KW - Ca pool
KW - Carbachol
KW - Hippocampus
KW - Long-term potentiation
KW - NMDA receptor
KW - Protein kinase
UR - http://www.scopus.com/inward/record.url?scp=0027484897&partnerID=8YFLogxK
U2 - 10.1016/0304-3940(93)90586-A
DO - 10.1016/0304-3940(93)90586-A
M3 - Article
C2 - 7510053
AN - SCOPUS:0027484897
SN - 0304-3940
VL - 162
SP - 165
EP - 168
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 1-2
ER -