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Volume 17, Number 1,
Issue of January 1, 1997
pp. 107-116
Copyright ©1997 Society for Neuroscience
A Direct Comparison of the Single-Channel Properties of Synaptic
and Extrasynaptic NMDA Receptors
Received July 8, 1996; revised Sept. 30, 1996; accepted Oct. 18, 1996.
Beverley A. Clark,
Mark Farrant, and
Stuart G. Cull-Candy
Department of Pharmacology, University College London, London WC1E
6BT, United Kingdom
The assumption that synaptic and extrasynaptic glutamate receptors
are similar underpins many studies that have sought to relate the
behavior of channels in excised patches to the macroscopic properties
of the EPSC. We have examined this issue for NMDA receptors in
cerebellar granule cells, the small size of which allows the opening of
individual synaptic NMDA channels to be resolved directly. We have used
whole-cell patch-clamp recordings to determine the conductance and open
time of NMDA channels activated during the EPSC and used cell-attached
and outside-out recordings to examine NMDA receptors in somatic
membrane. Conductance and open time of synaptic channels were
indistinguishable from those of extrasynaptic channels in cell-attached
patches. However, the channel conductance in outside-out patches was
20% lower than in cell-attached recordings. This change was partially
reduced by dantrolene and phalloidin, suggesting that it may involve
depolymerization of actin following Ca2+ release from
intracellular stores. Our results demonstrate that synaptic and
extrasynaptic NMDA receptors have similar microscopic properties.
However, NMDA channel conductance is reduced following the formation of
an outside-out patch.
Key words:
cerebellum;
granule cell;
patch clamp;
NMDA;
single
channel;
synaptic;
extrasynaptic
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