Carbachol can potentiate N-methyl-d-aspartate responses in the rat hippocampus by a staurosporine and thapsigargin-insensitive mechanism

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 - https://www.scopus.com/pages/publications/0027484897

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 -