Channel kinetics determine the time course of NMDA receptor-mediated synaptic currents

Nature ◽  
1990 ◽  
Vol 346 (6284) ◽  
pp. 565-567 ◽  
Author(s):  
Robin A. J. Lester ◽  
John D. Clements ◽  
Gary L. Westbrook ◽  
Craig E. Jahr
Keyword(s):  
Nmda Receptor ◽  
Time Course ◽  
Channel Kinetics ◽  
Synaptic Currents

NMDA-Dependent Currents in Granule Cells of the Dentate Gyrus Contribute to Induction but Not Permanence of Kindling

1999 ◽  
Vol 81 (2) ◽  
pp. 564-574 ◽  
Author(s):  
Ümit Sayin ◽  
Paul Rutecki ◽  
Thomas Sutula
Keyword(s):  
Nmda Receptor ◽  
Dentate Gyrus ◽  
Time Course ◽  
Granule Cells ◽  
Receptor Activation ◽  
Perforant Path ◽  
Synaptic Current ◽  
Synaptic Currents ◽  
Class V ◽  
Dependent Component

NMDA-dependent currents in granule cells of the dentate gyrus contribute to induction but not permanence of kindling. Single-electrode voltage-clamp techniques and bath application of the N-methyl-d-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV) were used to study the time course of seizure-induced alterations in NMDA-dependent synaptic currents in granule cells of the dentate gyrus in hippocampal slices from kindled and normal rats. In agreement with previous studies, granule cells from kindled rats examined within 1 wk after the last of 3 or 30–35 generalized tonic-clonic (class V) seizures demonstrated an increase in the NMDA receptor–dependent component of the perforant path–evoked synaptic current. Within 1 wk of the last kindled seizure, NMDA-dependent charge transfer underlying the perforant path–evoked current was increased by 63–111% at a holding potential of −30 mV. In contrast, the NMDA-dependent component of the perforant-evoked current in granule cells examined at 2.5–3 mo after the last of 3 or 90–120 class V seizures did not differ from age-matched controls. Because the seizure-induced increases in NMDA-dependent synaptic currents declined toward control values during a time course of 2.5–3 mo, increases in NMDA-dependent synaptic transmission cannot account for the permanent susceptibility to evoked and spontaneous seizures induced by kindling. The increase in NMDA receptor–dependent transmission was associated with the induction of kindling but was not responsible for the maintenance of the kindled state. The time course of alterations in NMDA-dependent synaptic current and the dependence of the progression of kindling and kindling-induced mossy fiber sprouting on repeated NMDA receptor activation are consistent with the possibility that the NMDA receptor is part of a transmembrane signaling pathway that induces long-term cellular alterations and circuit remodeling in response to repeated seizures, but is not required for permanent seizure susceptibility in circuitry altered by kindling.

The time course of NMDA receptor-mediated synaptic currents

1995 ◽  
pp. 206-218 ◽  
Author(s):  
ROBIN A. J. LESTER ◽  
JOHN D. CLEMENTS ◽  
GANG TONG ◽  
GARY L. WESTBROOK ◽  
CRAIG E. JAHR
Keyword(s):  
Nmda Receptor ◽  
Time Course ◽  
Synaptic Currents

Development of Glutamatergic Synaptic Activity in Cultured Spinal Neurons

2000 ◽  
Vol 83 (2) ◽  
pp. 659-670 ◽  
Author(s):  
Antoine Robert ◽  
James R. Howe ◽  
Stephen G. Waxman
Keyword(s):  
Nmda Receptor ◽  
Ampa Receptor ◽  
Time Course ◽  
Synaptic Activity ◽  
Spinal Neurons ◽  
Glutamatergic Synapses ◽  
Synaptic Currents ◽  
Sequence Of Events ◽  
Short Times

The development of glutamatergic synapses involves a sequence of events that are still not well understood. We have studied the time course of the development of glutamatergic synapses in cultured spinal neurons by characterizing spontaneous synaptic currents recorded from cells maintained in vitro for different times. At short times in culture (2 days in vitro; DIV2), spontaneous synaptic activity consisted almost solely of N-methyl-d-aspartate (NMDA) receptor (NMDAR) openings. In contrast, older neurons (DIV5 to DIV8) displayed clear α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR)–mediated synaptic currents, while the NMDAR-mediated activity remained small. Between 8 and 14 days in vitro there was a large increase in the density of synaptically activated NMDARs, although there was no significant increase in the density of the NMDAR-mediated current activated by exogenous glutamate. The results indicate that there is a switch in NMDAR targeting from somatic to synaptic regions during the course of the second in vitro week. Finally, our results support the conclusion that the spontaneous synaptic activity displayed in culture depends on ongoing NMDAR-mediated activity, even when the expression of synaptic NMDARs is low.

Modulation of the time course of fast EPSCs and glutamate channel kinetics by aniracetam

Science ◽  
1991 ◽  
Vol 254 (5029) ◽  
pp. 288-290
Author(s):  
CM Tang ◽  
QY Shi ◽  
A Katchman ◽  
G Lynch
Keyword(s):  
Central Nervous System ◽  
Nmda Receptor ◽  
Time Course ◽  
Single Channel ◽  
Excitatory Synapses ◽  
Channel Kinetics ◽  
Synaptic Release ◽  
Nootropic Agent ◽  
Nmda Channels ◽  
Kinetics Of

It is generally accepted that glutamate serves as the neurotransmitter at most excitatory synapses in the mammalian central nervous system (CNS). Synaptic release of glutamate may trigger a fast and a slow excitatory postsynaptic current (EPSC). The slow EPSC is mediated by N-methyl-D-aspartate (NMDA) receptor channels, whereas the fast EPSC is mediated by non-NMDA receptor channels. The nootropic agent aniracetam selectively and reversibly slows the desensitization kinetics of non-NMDA channels and lengthens their single-channel open times. Antiracetam also modulates the kinetics of the fast EPSC in a manner that mirrors its action on the kinetics of the non-NMDA channels. These results support the hypothesis that the properties of the non-NMDA glutamate channels rather than the rate of neurotransmitter clearance are the primary determinants of the kinetics of the fast EPSC in the mammalian CNS.

scholarly journals Androgens Modulate NMDA Receptor–Mediated EPSCs in the Zebra Finch Song System

1999 ◽  
Vol 82 (5) ◽  
pp. 2221-2234 ◽  
Author(s):  
Stephanie A. White ◽  
Frederick S. Livingston ◽  
Richard Mooney
Keyword(s):  
Nmda Receptor ◽  
Synaptic Transmission ◽  
Time Course ◽  
Song Learning ◽  
Lateral Part ◽  
Spine Density ◽  
Song System ◽  
Decay Times ◽  
Soma Size

Androgens potently regulate the development of learned vocalizations of songbirds. We sought to determine whether one action of androgens is to functionally modulate the development of synaptic transmission in two brain nuclei, the lateral part of the magnocellular nucleus of the anterior neostriatum (LMAN) and the robust nucleus of the archistriatum (RA), that are critical for song learning and production. We focused on N-methyl-d-aspartate–excitatory postsynaptic currents (NMDA-EPSCs), because NMDA receptor activity in LMAN is crucial to song learning, and because the LMAN synapses onto RA neurons are almost entirely mediated by NMDA receptors. Whole cell recordings from in vitro brain slice preparations revealed that the time course of NMDA-EPSCs was developmentally regulated in RA, as had been shown previously for LMAN. Specifically, in both nuclei, NMDA-EPSCs become faster over development. We found that this developmental transition can be modulated by androgens, because testosterone treatment of young animals caused NMDA-EPSCs in LMAN and RA to become prematurely fast. These androgen-induced effects were limited to fledgling and juvenile periods and were spatially restricted, in that androgens did not accelerate developmental changes in NMDA-EPSCs recorded in a nonsong area, the Wulst. To determine whether androgens had additional effects on LMAN or RA neurons, we examined several other physiological and morphological parameters. In LMAN, testosterone affected α-amino-3-hydroxy-5-methyl-4-isoxazoleproprianate–EPSC (AMPA-EPSC) decay times and the ratio of peak synaptic glutamate to AMPA currents, as well as dendritic length and spine density but did not alter soma size or dendritic complexity. In contrast, testosterone did not affect any of these parameters in RA, which demonstrates that exogenous androgens can have selective actions on different song system neurons. These data are the first evidence for any effect of sex steroids on synaptic transmission within the song system. Our results support the idea that endogenous androgens limit sensitive periods for song learning by functionally altering synaptic transmission in song nuclei.

A Fast Synaptic Potential Mediated by NMDA and Non-NMDA Receptors

1997 ◽  
Vol 78 (5) ◽  
pp. 2693-2706 ◽  
Author(s):  
Laura R. Wolszon ◽  
Alberto E. Pereda ◽  
Donald S. Faber
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Resting Potential ◽  
Repetitive Firing ◽  
Physiological Data ◽  
Receptor Subtypes ◽  
Excitatory Postsynaptic Potential ◽  
Synaptic Potential ◽  
Synaptic Currents ◽  
Fast Kinetics

Wolszon, Laura R., Alberto E. Pereda, and Donald S. Faber. A fast synaptic potential mediated by NMDA and non-NMDA receptors. J. Neurophysiol. 78: 2693–2706, 1997. Excitatory synaptic transmission in the CNS often is mediated by two kinetically distinct glutamate receptor subtypes that frequently are colocalized, the N-methyl-d-aspartate (NMDA) and non-NMDA receptors. Their synaptic currents are typically very slow and very fast, respectively. We examined the pharmacological and physiological properties of chemical excitatory transmission at the mixed electrical and chemical synapses between auditory afferents and the goldfish Mauthner cell, in vivo. Previous physiological data have suggested the involvement of glutamate receptors in this fast excitatory postsynaptic potential (EPSP), the chemical component of which decays with a time constant of <2 ms. We demonstrate here that the pharmacological and voltage-dependent characteristics of the synaptic currents are consistent with glutamatergic transmission and that both NMDA and non-NMDA receptors are involved. The two components surprisingly exhibit quite similar kinetics even at resting potential, with the NMDA response being only slightly slower. Due to its fast kinetics and characteristic voltage dependence, NMDA receptor-mediated transmission at these first-order synapses contributes significantly to paired pulse and frequency-dependent facilitation of successive fast EPSPs during high-frequency repetitive firing, a presynaptic impulse pattern that induces activity-dependent homosynaptic changes in both electrical and chemical transmission. Thus NMDA receptor kinetics in this intact preparation are suited to its functional requirements, namely speed of information transmission and the ability to trigger changes in synaptic efficacy.

Glycine regulation of synaptic NMDA receptors in hippocampal neurons

1996 ◽  
Vol 76 (5) ◽  
pp. 3415-3424 ◽  
Author(s):  
K. S. Wilcox ◽  
R. M. Fitzsimonds ◽  
B. Johnson ◽  
M. A. Dichter
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Hippocampal Neurons ◽  
Time Course ◽  
Hippocampal Slices ◽  
Maximal Effect ◽  
Patch Clamp Technique ◽  
Whole Cell Patch Clamp ◽  
Dissociated Cell Culture ◽  
Cultured Hippocampal Neurons

1. Although glycine has been identified as a required coagonist with glutamate at N-methyl-D-aspartate (NMDA) receptors, the understanding of glycine's role in excitatory synaptic neurotransmission is quite limited. In the present study, we used the whole cell patch-clamp technique to examine the ability of glycine to regulate current flow through synaptic NMDA receptors at excitatory synapses between cultured hippocampal neurons and in acutely isolated hippocampal slices. 2. These studies demonstrate that the glycine modulatory site on the synaptic NMDA receptor is not saturated under baseline conditions and that increased glycine concentrations can markedly increased NMDA-receptor-mediated excitatory postsynaptic currents (EPSCs) in hippocampal neurons in both dissociated cell culture and in slice. Saturation of the maximal effect of glycine takes place at different concentrations for different cells in culture, suggesting the presence of heterogenous NMDA receptor subunit compositions. 3. Bath-applied glycine had no effect on the time course of EPSCs in either brain slice or culture, indicating that desensitization of the NMDA receptor is not prevented by glycine over the time course of an EPSC. 4. When extracellular glycine concentration is high, all miniature EPSCs recorded in the cultured hippocampal neurons contained NMDA components, indicating that segregation of non-NMDA receptors at individual synaptic boutons does not occur.

scholarly journals The calcium-activated potassium channels of turtle hair cells.

1995 ◽  
Vol 105 (1) ◽  
pp. 49-72 ◽  
Author(s):  
J J Art ◽  
Y C Wu ◽  
R Fettiplace
Keyword(s):  
Resonant Frequency ◽  
Time Constant ◽  
Hair Cells ◽  
Time Course ◽  
Voltage Dependence ◽  
Bk Channels ◽  
Hair Bundle ◽  
Sk Channels ◽  
Channel Kinetics ◽  
Ca Current

A major factor determining the electrical resonant frequency of turtle cochlear hair cells is the time course of the Ca-activated K current (Art, J. J., and R. Fettiplace. 1987. Journal of Physiology. 385:207-242). We have examined the notion that this time course is dictated by the K channel kinetics by recording single Ca-activated K channels in inside-out patches from isolated cells. A hair cell's resonant frequency was estimated from its known correlation with the dimensions of the hair bundle. All cells possess BK channels with a similar unit conductance of approximately 320 pS but with different mean open times of 0.25-12 ms. The time constant of relaxation of the average single-channel current at -50 mV in 4 microM Ca varied between cells from 0.4 to 13 ms and was correlated with the hair bundle height. The magnitude and voltage dependence of the time constant agree with the expected behavior of the macroscopic K(Ca) current, whose speed may thus be limited by the channel kinetics. All BK channels had similar sensitivities to Ca which produced half-maximal activation for a concentration of approximately 2 microM at +50 mV and 12 microM at -50 mV. We estimate from the voltage dependence of the whole-cell K(Ca) current that the BK channels may be fully activated at -35 mV by a rise in intracellular Ca to 50 microM. BK channels were occasionally observed to switch between slow and fast gating modes which raises the possibility that the range of kinetics of BK channels observed in different hair cells reflects a common channel protein whose kinetics are regulated by an unidentified intracellular factor. Membrane patches also contained 30 pS SK channels which were approximately 5 times more Ca-sensitive than BK channels at -50 mV. The SK channels may underlie the inhibitory synaptic potential produced in hair cells by efferent stimulation.

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