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Direct effects of calmodulin on NMDA receptor single-channel gating in rat hippocampal granule cells.

NMDA receptors are glutamate-sensitive ion channel receptors that mediate excitatory synaptic transmission and are widely implicated in synaptic plasticity and integration of synaptic activity in the CNS. This is in part attributable to the high calcium permeability of the ion channel, which allows... Full description

Journal Title: The Journal of neuroscience : the official journal of the Society for Neuroscience October 15, 2002, Vol.22(20), pp.8860-8868
Main Author: Rycroft, Beth K
Other Authors: Gibb, Alasdair J
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1529-2401
Link: http://search.proquest.com/docview/72191824/?pq-origsite=primo
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title: Direct effects of calmodulin on NMDA receptor single-channel gating in rat hippocampal granule cells.
format: Article
creator:
  • Rycroft, Beth K
  • Gibb, Alasdair J
subjects:
  • Animals–Pharmacology
  • Calmodulin–Drug Effects
  • Cytoplasmic Granules–Physiology
  • Hippocampus–Drug Effects
  • In Vitro Techniques–Physiology
  • Ion Channel Gating–Drug Effects
  • Neuronal Plasticity–Drug Effects
  • Neurons–Metabolism
  • Patch-Clamp Techniques–Physiology
  • Rats–Drug Effects
  • Rats, Sprague-Dawley–Metabolism
  • Receptor Aggregation–Physiology
  • Receptors, N-Methyl-D-Aspartate–Physiology
  • Synaptic Transmission–Physiology
  • Time Factors–Physiology
  • Calmodulin
  • Receptors, N-Methyl-D-Aspartate
ispartof: The Journal of neuroscience : the official journal of the Society for Neuroscience, October 15, 2002, Vol.22(20), pp.8860-8868
description: NMDA receptors are glutamate-sensitive ion channel receptors that mediate excitatory synaptic transmission and are widely implicated in synaptic plasticity and integration of synaptic activity in the CNS. This is in part attributable to the high calcium permeability of the ion channel, which allows receptor activation to influence the intracellular calcium concentration and also the slow time course of NMDA receptor-mediated synaptic currents. NMDA receptor activity is also regulated by the intracellular calcium concentration through activation of various calcium-dependent proteins, including calmodulin, calcineurin, protein kinase C, and alpha-actinin-2. Here, we have shown that calmodulin reduces the duration of native NMDA receptor single-channel openings from 3.5 +/- 0.6 msec to 1.71 +/- 0.2 msec in agreement with previous studies on recombinant NMDA receptors (Ehlers et al., 1996). NMDA receptor single-channel amplitudes and shut times were not affected. However, calmodulin reduced the duration of groups of channel openings called superclusters, which determine the slow time course of synaptic currents, from 121 +/- 25.4 msec to 60.4 +/- 11.6 msec. In addition, total open time, number of channel openings, and charge transfer per supercluster were all reduced by calmodulin. A 68% decrease in charge transfer per supercluster suggests that calmodulin activation will significantly reduce calcium influx during synaptic transmission. These results suggest that calmodulin-dependent inhibition of NMDA receptors will reduce the amplitude and time course of excitatory synaptic currents and thus affect synaptic plasticity and integration of synaptic activity in the CNS.
language: eng
source:
identifier: E-ISSN: 1529-2401
fulltext: fulltext
issn:
  • 15292401
  • 1529-2401
url: Link


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titleDirect effects of calmodulin on NMDA receptor single-channel gating in rat hippocampal granule cells.
creatorRycroft, Beth K ; Gibb, Alasdair J
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subjectAnimals–Pharmacology ; Calmodulin–Drug Effects ; Cytoplasmic Granules–Physiology ; Hippocampus–Drug Effects ; In Vitro Techniques–Physiology ; Ion Channel Gating–Drug Effects ; Neuronal Plasticity–Drug Effects ; Neurons–Metabolism ; Patch-Clamp Techniques–Physiology ; Rats–Drug Effects ; Rats, Sprague-Dawley–Metabolism ; Receptor Aggregation–Physiology ; Receptors, N-Methyl-D-Aspartate–Physiology ; Synaptic Transmission–Physiology ; Time Factors–Physiology ; Calmodulin ; Receptors, N-Methyl-D-Aspartate
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descriptionNMDA receptors are glutamate-sensitive ion channel receptors that mediate excitatory synaptic transmission and are widely implicated in synaptic plasticity and integration of synaptic activity in the CNS. This is in part attributable to the high calcium permeability of the ion channel, which allows receptor activation to influence the intracellular calcium concentration and also the slow time course of NMDA receptor-mediated synaptic currents. NMDA receptor activity is also regulated by the intracellular calcium concentration through activation of various calcium-dependent proteins, including calmodulin, calcineurin, protein kinase C, and alpha-actinin-2. Here, we have shown that calmodulin reduces the duration of native NMDA receptor single-channel openings from 3.5 +/- 0.6 msec to 1.71 +/- 0.2 msec in agreement with previous studies on recombinant NMDA receptors (Ehlers et al., 1996). NMDA receptor single-channel amplitudes and shut times were not affected. However, calmodulin reduced the duration of groups of channel openings called superclusters, which determine the slow time course of synaptic currents, from 121 +/- 25.4 msec to 60.4 +/- 11.6 msec. In addition, total open time, number of channel openings, and charge transfer per supercluster were all reduced by calmodulin. A 68% decrease in charge transfer per supercluster suggests that calmodulin activation will significantly reduce calcium influx during synaptic transmission. These results suggest that calmodulin-dependent inhibition of NMDA receptors will reduce the amplitude and time course of excitatory synaptic currents and thus affect synaptic plasticity and integration of synaptic activity in the CNS.
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