European Jowtral of Pharmacology, 0 1991 Elsevier
205 ( 1991) 327-328
327
Science Publishers B.V. All rights reserved 0014-2999/91/$03.50
EJP 0326R
Rapid communication
Selective activation of quisqualate metabotropic receptor potentiates N not AMPA responses
but
L. Aniksztejn, P. Bregestovski and Y. Ben-Ari INSERM
U29, HGpital de Port-Royrrl, 123 Boulevard de Port-Royal,
Received
6 November
1991. accepted
Second messenger systems modulate neural excitability by modifying voltage- and ligand-gated channels. A recent report has shown that AMPA (cu-amino3-hydrorql-5methylisoxazole-4-propionic acid) receptors which mediate the fast component of the excitatory postsynaptic potentials in hippocampal neurons are upregulated by CAMP-dependent protein kinase (PKA) in hippocampal neurons (Wang et al., 1991). Two other subtypes of excitatory amino receptors play a central role in neural plasticity: the N-methyl-Daspartate receptor channel complex (NMDA), which is permeable to Ca*+ and the metabotropic receptor (Qr), the activation of which stimulates phospholipase C and generates diacylglycerol and IPj, leading to activation of protein kinase C and mobilization of Ca2+ from intracellular stores Gchoepp et al., 1990). We now report that selective activation of metabotropic receptor potentiates NMDA but not AMPA currents in hippocampal neurons. Single electrode voltage-clamp recordings have been performed in CA1 pyramidal neurons of adult hippocampal slices maintained in fully submerged conditions (for details see Aniksztejn and Ben-Ari, 1991). The microelectrodes were filled with CsCl (3 M) to block potassium channels and to increase space clamp. As shown in fig. 1, bath application of NMDA (10 PM, 90 s) generated an inward current of 360 pA. Bath application of the selective metabotropic agonist lS,3R-ACPD (lS,3R-1-amino-1,3qclopentanedicarboxylic acid) for 240 s generated a small steady inward current (70 PA). At this stage, NMDA was coapplied with lS$R-ACPD for 90 s, and produced a much larger inward current (1200 pAI. These effects were
11November
a
c
NMDA
D lS.3R-ACPO
1. Potentiation
metabotropic
Port-Royal,
75014 Paris. France.
INSERM
U29,
123 Boulevard
de
NMDA
NMOA ____I__
of NMDA
currents
by selective
activation
(QP) receptors. (a. b. c) Inward currents generated
CA1 pyramidal to: Y. Ben-Ari,
1991
reversible since application (5 min later) of NMDA generated a response similar to the control (pre-ACPD) situation (320 pAI. Similar observations were made in 6 neurons (potentiation of 215 f 80%, mean _+SD.), including three neurons in which lS,3R-ACPD did not generate an inward current. Furthermore, similar observations were made in four neurons in which TEA (10 mM) was bath applied. Under these conditions, lS,3R-ACPD did not induce a significant inward current (not shown). In contrast, AMPA responses recorded from the same neurons were not potentiated by IS,SR-ACPD when the same protocol was used (n = 3, not shown). The present study demonstrates a selective enhancement of NMDA but not AMPA responses by activation of metabotropic receptors. The effects of 1S,3R-ACPD are probably mediated via protein kinase C, since ti) activation of p opioid receptors increases NMDA currents, an effect mediated by activation of PKC (Chen and Huang, 1991) and (ii) preliminary observations
Fig.
Correspondence
75014 Paris, France
neuron by bath application
of NMDA
(10 pM.
of in a
90 S)
before (a), during fb) and 5 min after fc) applications of IS.3R-ACPD (50 ~kf,
240 s). Holding potential (Vu)
-61
mV.
L. Aniksrtejn and \‘. Ben-Ari. 1991. Novel form of long term potentiation produced by a K * channel blocker in the hippocampus. Nature hi’. 34Y. Li Chrn and Li-yen Mae Huar;~. 1YY1. Sustained potentiation of NMDA receptor-mediated glutamate responses through activation of protein kinase C hy a g opioid, Neuron 7. 319. S. Otani and Y. Ben-Ari. 1991. Metabotropic receptor-mediated long-term potentiation in rat hippocampal slices. Eur. J. Pharmacol. 205. 23. D. Schoepp. J. Bockaert and F. Sladeczek. 1990. Pharmalogical and functional characteristics of metahotropic excitatory amino acid receptors. Trends Pharmacol. Sci. I I. 508. L.Y. Wang. M.W. Salter and J.F. Mac Donald, 1991. Regulation o: kainate receptors hy cAMP dependent protein kinase and phosphatases. Science 33. 1131.
205 ( 1991) 327-328
327
Science Publishers B.V. All rights reserved 0014-2999/91/$03.50
EJP 0326R
Rapid communication
Selective activation of quisqualate metabotropic receptor potentiates N not AMPA responses
but
L. Aniksztejn, P. Bregestovski and Y. Ben-Ari INSERM
U29, HGpital de Port-Royrrl, 123 Boulevard de Port-Royal,
Received
6 November
1991. accepted
Second messenger systems modulate neural excitability by modifying voltage- and ligand-gated channels. A recent report has shown that AMPA (cu-amino3-hydrorql-5methylisoxazole-4-propionic acid) receptors which mediate the fast component of the excitatory postsynaptic potentials in hippocampal neurons are upregulated by CAMP-dependent protein kinase (PKA) in hippocampal neurons (Wang et al., 1991). Two other subtypes of excitatory amino receptors play a central role in neural plasticity: the N-methyl-Daspartate receptor channel complex (NMDA), which is permeable to Ca*+ and the metabotropic receptor (Qr), the activation of which stimulates phospholipase C and generates diacylglycerol and IPj, leading to activation of protein kinase C and mobilization of Ca2+ from intracellular stores Gchoepp et al., 1990). We now report that selective activation of metabotropic receptor potentiates NMDA but not AMPA currents in hippocampal neurons. Single electrode voltage-clamp recordings have been performed in CA1 pyramidal neurons of adult hippocampal slices maintained in fully submerged conditions (for details see Aniksztejn and Ben-Ari, 1991). The microelectrodes were filled with CsCl (3 M) to block potassium channels and to increase space clamp. As shown in fig. 1, bath application of NMDA (10 PM, 90 s) generated an inward current of 360 pA. Bath application of the selective metabotropic agonist lS,3R-ACPD (lS,3R-1-amino-1,3qclopentanedicarboxylic acid) for 240 s generated a small steady inward current (70 PA). At this stage, NMDA was coapplied with lS$R-ACPD for 90 s, and produced a much larger inward current (1200 pAI. These effects were
11November
a
c
NMDA
D lS.3R-ACPO
1. Potentiation
metabotropic
Port-Royal,
75014 Paris. France.
INSERM
U29,
123 Boulevard
de
NMDA
NMOA ____I__
of NMDA
currents
by selective
activation
(QP) receptors. (a. b. c) Inward currents generated
CA1 pyramidal to: Y. Ben-Ari,
1991
reversible since application (5 min later) of NMDA generated a response similar to the control (pre-ACPD) situation (320 pAI. Similar observations were made in 6 neurons (potentiation of 215 f 80%, mean _+SD.), including three neurons in which lS,3R-ACPD did not generate an inward current. Furthermore, similar observations were made in four neurons in which TEA (10 mM) was bath applied. Under these conditions, lS,3R-ACPD did not induce a significant inward current (not shown). In contrast, AMPA responses recorded from the same neurons were not potentiated by IS,SR-ACPD when the same protocol was used (n = 3, not shown). The present study demonstrates a selective enhancement of NMDA but not AMPA responses by activation of metabotropic receptors. The effects of 1S,3R-ACPD are probably mediated via protein kinase C, since ti) activation of p opioid receptors increases NMDA currents, an effect mediated by activation of PKC (Chen and Huang, 1991) and (ii) preliminary observations
Fig.
Correspondence
75014 Paris, France
neuron by bath application
of NMDA
(10 pM.
of in a
90 S)
before (a), during fb) and 5 min after fc) applications of IS.3R-ACPD (50 ~kf,
240 s). Holding potential (Vu)
-61
mV.
L. Aniksrtejn and \‘. Ben-Ari. 1991. Novel form of long term potentiation produced by a K * channel blocker in the hippocampus. Nature hi’. 34Y. Li Chrn and Li-yen Mae Huar;~. 1YY1. Sustained potentiation of NMDA receptor-mediated glutamate responses through activation of protein kinase C hy a g opioid, Neuron 7. 319. S. Otani and Y. Ben-Ari. 1991. Metabotropic receptor-mediated long-term potentiation in rat hippocampal slices. Eur. J. Pharmacol. 205. 23. D. Schoepp. J. Bockaert and F. Sladeczek. 1990. Pharmalogical and functional characteristics of metahotropic excitatory amino acid receptors. Trends Pharmacol. Sci. I I. 508. L.Y. Wang. M.W. Salter and J.F. Mac Donald, 1991. Regulation o: kainate receptors hy cAMP dependent protein kinase and phosphatases. Science 33. 1131.
