NMDA receptor agonists selectively block N-type calcium channels in hippocampal neurons

Chernevskaya, N. I.; Obukhov, Alexander G.; Krishtal, O. A.

doi:10.1038/349418a0

Cited by 65 publications

(23 citation statements)

References 26 publications

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“…Furthermore, NMDA generated inward current but had no significant effect on synaptic transmission. These findings are similar to those found in hippocampal culture (Forsythe & Clements, 1990) (Chernevskaya, Obukhov & Krishtal, 1991) (Harris & Cotman, 1983;Cotman et al 1986;Forsythe & Clements, 1990).…”

Section: Discussionsupporting

confidence: 81%

Agonists at metabotropic glutamate receptors presynaptically inhibit EPSCs in neonatal rat hippocampus.

Baskys

Malenka

1991

The Journal of Physiology

420

221

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SUMMARY1. The effects of metabotropic glutamate receptor agonists on excitatory synaptic transmission in the CAI region of rat hippocampal slices (11-30 days) were studied using extracellular and whole-cell patch-clamp recording techniques.2. Trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD; 25-100 ,sM) reversibly depressed excitatory postsynaptic currents (EPSCs) without affecting presynaptic fibre excitability or EPSC reversal potential.3. Ibotenate (25 ,lM) or L-glutamate (250 /1M), in the presence of the N-methyl-Daspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonovaleric acid (APV, 50-75 JLM), depressed the EPSC amplitude while inducing no detectable inward current. L-2-Amino-4-phosphonobutyrate (L-AP4, 25-100 /tM), the phosphonic derivative of glutamate, also depressed EPSC amplitude and caused no detectable inward current.4. The NMDA receptor-mediated component of the EPSC recorded in the presence of the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20-30 ,tM) was depressed by trans-ACPD, L-AP4, or quisqualate (1-2 /,M).5. The response to ionophoretic application of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) was unaffected by trans-ACPD or L-AP4 although the simultaneously recorded EPSC was strongly depressed. In addition, paired-pulse facilitation (50-75 ms interstimulus interval) was reversibly enhanced by trans-ACPD or L-AP4. These results indicate that the depression of synaptic transmission likely was mediated by a presynaptic 'autoreceptor'.6. The effects of trans-ACPD or L-AP4 on synaptic transmission decreased significantly over ages 12-30 days and were minimal in adult ( > 80 days) slices.7. The depression of synaptic transmission caused by trans-ACPD or L-AP4 was not altered following the induction of long-term potentiation (LTP).

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Section: Discussionsupporting

confidence: 81%

Agonists at metabotropic glutamate receptors presynaptically inhibit EPSCs in neonatal rat hippocampus.

Baskys

Malenka

1991

The Journal of Physiology

420

221

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“…These data suggest that NMDA receptors play a role in the regulation of GABAergic transmission. Overall, these data are consistent with previous demonstrations that presynaptic NMDA receptors contribute to NMDA-mediated phenomena in other regions of the nervous system (58)(59)(60)(61)(62)(63)(64).…”

supporting

confidence: 82%

Localization of NMDA receptors in the cerebral cortex: a schematic overview

Conti¹

1997

Braz J Med Biol Res

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The fundamental role of N-methyl-D-aspartate (NMDA) receptors in many cortical functions has been firmly defined, as has its involvement in a number of neurological and psychiatric diseases. However, until recently very little was known about the anatomical localization of NMDA receptors in the cerebral cortex of mammals. The recent application of molecular biological techniques to the study of NMDA receptors has provided specific tools which have greatly expanded our understanding of the localization of NMDA receptors in the cerebral cortex. In particular, immunocytochemical studies on the distribution of cortical NMDA receptors have shown that NMDA receptors are preferentially localized on dendritic spines, have disclosed an unknown fraction of presynaptic NMDA receptors on both excitatory and inhibitory axon terminals, and demonstrated that cortical astrocytes do express NMDA receptors. These studies suggest that the effects induced by the activation of NMDA receptors are not due solely to the opening of NMDA channels on neuronal postsynaptic membranes, as previously assumed, but that the activation of presynaptic and glial NMDA receptors may mediate part of these effects.Correspondence

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“…While we have observed that NMDA elicits an increase in Ca2+ channel activity in CA1 pyramidal neurons, it was recently reported that NMDA receptor agonists reduced a portion of the macroscopic Ca2" current in CA1 pyramidal neurons isolated from young rats (37). In that study, however, the neurons were dialyzed with cAMP, ATP, and GTP, which would have occluded any NMDA-mediated increases in cAMP and subsequent changes in Ca2+ channel activity.…”

Section: Discussionmentioning

confidence: 89%

N-methyl-D-aspartate receptor activation increases cAMP levels and voltage-gated Ca2+ channel activity in area CA1 of hippocampus.

Chetkovich

Gray

Johnston³

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

246

111

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Tetanic stimulation of the Schaffer collateral inputs into area CA1 of the hippocampus causes N-methyl-Daspartate (NMDA) receptor activation, an effect that contributes to the induction of long-term potentiation (LTP) in this region. The present studies demonstrate that LTP-inducing tetanic stimulation in rat hippocampal area CA1 elicited increased levels of cAMP. The elevation of cAMP was blocked by the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV). Bath application of NMDA also resulted in an increase in cAMP in CA1, an effect that was blocked by both APV and removal of extracellular Ca2+. These frndings suggest that activation of NMDA receptors elicits a Ca2+-dependent increase in cAMP, and taken together with the data from tetanic stimulation, suggest that NMDA-receptor-mediated increases in cAMP could play a role in the induction of LTP in area CAL. One role for cAMP may be to increase Ca2+ influx through voltage-gated Ca21 channels, as it was observed that application of either Long-term potentiation of synaptic transmission (LTP) is a robust form of synaptic plasticity that is a strong candidate mechanism for learning and memory in the mammalian brain (for reviews, see refs. 1 and 2). The induction of the most commonly studied form of LTP in area CA1 of the hippocampus requires activation of N-methyl-D-aspartate (NMDA) receptors (3, 4). NMDA receptor activation allows the influx of Ca2+ into neurons, an effect that has been causally linked to the induction of LTP (5-8). The biochemical sequelae of the NMDA-receptor-mediated Ca2+ influx, however, are not well characterized. Available evidence suggests that the activation of Ca2+-dependent protein kinases contributes to the induction of LTP (9-12). Ca2+ is a pleuripotent second messenger, and many biochemical effects of Ca2' are well documented in the central nervous system, including activation, through calmodulin, ofadenylyl cyclase (13,14). In the experiments reported here, we tested the hypothesis that NMDA receptor activation increases cAMP in area CA1 of the hippocampus and that a physiological consequence of increased cAMP is an increase in the activity of voltage-gated Ca2+ channels. (1) in the CA1 region were monitored for 20 min to assure a stable baseline. Tetanic stimulation consisted of three one-s trains of stimuli (100 Hz) every 5 s at the minimum stimulus current needed to elicit a maximal population excitatory postsynaptic potential (EPSP). This stimulus was sufficient to induce LTP in >90%o of slices (20 of 22). LTP was defined as a 20% or greater increase in initial EPSP slope, or in initial experiments it was defined as a 30% or greater increase in population spike amplitude. When present, DL-2-amino-5-phosphonovaleric acid (APV) was 50 ,AM in the bath, a concentration that was found to block LTP induced by this stimulus paradigm (n = 6). MATERIALS AND METHODSMeasurement of cAMP. Slices were allowed to adjust to the recording chamber for 1.5-2 hr to allow cAMP levels to stabilize (15). Slices were removed fr...

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NMDA receptor agonists selectively block N-type calcium channels in hippocampal neurons

Cited by 65 publications

References 26 publications

Agonists at metabotropic glutamate receptors presynaptically inhibit EPSCs in neonatal rat hippocampus.

Agonists at metabotropic glutamate receptors presynaptically inhibit EPSCs in neonatal rat hippocampus.

Localization of NMDA receptors in the cerebral cortex: a schematic overview

N-methyl-D-aspartate receptor activation increases cAMP levels and voltage-gated Ca2+ channel activity in area CA1 of hippocampus.

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