The Journal of Neuroscience, October 15, 2002, 22(20):8860-8868
Direct Effects of Calmodulin on NMDA Receptor Single-Channel
Gating in Rat Hippocampal Granule Cells
Beth K.
Rycroft and
Alasdair J.
Gibb
Department of Pharmacology, University College London, London WC1E
6BT, United Kingdom
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 
-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.
Key words:
NMDA receptors; calmodulin; hippocampus; dentate gyrus; granule cells; postnatal development; rat brain; patch-clamp
Copyright © 2002 Society for Neuroscience 0270-6474/02/22208860-09$05.00/0
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