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Volume 17, Number 8,
Issue of April 15, 1997
pp. 2813-2824
Copyright ©1997 Society for Neuroscience
Reduction of K+ Uptake in Glia Prevents Long-Term
Depression Maintenance and Causes Epileptiform Activity
Received Sept. 3, 1996; revised Dec. 17, 1996; accepted Dec. 20, 1996.
Damir Janigro1,
Sonia Gasparini2,
Raimondo D'Ambrosio1, 2,
Guy McKhann
II1, and
Dario DiFrancesco2
1 Department of Neurological Surgery, University of
Washington, School of Medicine, Seattle, Washington 98104, and
2 Dipartimento di Fisiologia e Biochimica Generali,
Università degli Studi, 20132 Milano, Italy
Extracellular cesium causes synchronous, interictal-like bursting
and prevents maintenance of long-term depression (LTD) in the CA1
hippocampal region. We have investigated the cellular mechanisms
underlying cesium actions. Whole-cell recordings showed that brief (2 min) bath exposures to cesium caused pyramidal cell hyperpolarization
associated with decreased membrane conductance attributable to blockade
of an inward h-type current. After prolonged (>2 min) exposures, a
late depolarizing response was observed; this effect was not associated
with changes in cell membrane conductance. Recordings from interneurons
revealed that Ih is expressed in a subpopulation of cells
and that cesium effects on interneurons expressing Ih are
comparable to those observed in pyramidal cells. Consistent with this
effect, cesium decreased the early component of the IPSP recorded in
pyramidal cells. Interneurons lacking Ih were not affected
by cesium but developed a depolarizing response when drug applications
were paired to orthodromic stimulation. We concluded that cesium
actions on LTD and cesium-induced epileptiform activity were not
attributable exclusively to its direct effects on neurons. Recordings
from hippocampal slice astrocytes revealed that cesium interfered with
glial electrical responses during LTD induction. Cesium blocked glial
inwardly rectifying potassium channels and increased the amplitude and
duration of stimulation-evoked [K+]out
increases. Thus, the effects of cesium on CA1 synchronization and
synaptic plasticity appear to be mediated predominantly by blockade of
glial voltage-dependent potassium uptake.
Key words:
spatial buffering;
epilepsy;
synchronization;
astrocyte;
potassium;
extracellular space
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