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Volume 17, Number 16,
Issue of August 15, 1997
pp. 6133-6141
Copyright ©1997 Society for Neuroscience
High Intracellular Cl Concentrations Depress
G-Protein-Modulated Ionic Conductances
Received March 26, 1997; revised June 4, 1997; accepted June 6, 1997.
Robert A. Lenz,
Thomas A. Pitler, and
Bradley E. Alger
Department of Physiology, University of Maryland School of
Medicine, Baltimore, Maryland 21201
Numerous G-protein-modulated ionic conductances are present in
central neurons and play major roles in regulating neuronal excitability. Accordingly, endogenous factors that alter the operation of these conductances may have profound effects on neuronal function. We now report that several G-protein-modulated ionic conductances in
hippocampal neurons are very much altered when Cl
is the predominant anion in the recording electrode. We used both
sharp-electrode and whole-cell techniques in rat hippocampal slices to
determine whether hippocampal CA1 pyramidal cell properties are altered
by KCl-filled, as compared with KCH3SO3- or
K-gluconate-filled, electrodes. We studied the effects of the anions on
synaptically evoked GABAB responses and baclofen- and
serotonin-induced currents as well as on a voltage-activated cation
current, Ih. High intracellular concentrations of chloride
([Cl]i) depressed all the
responses without altering resting cell properties. Intermediate
[Cl]i reduced baclofen-induced
currents as well as Ih in a dose-dependent manner. In KCH3SO3-filled cells, equimolar
substitution of GTP S for Tris-GTP results in activation of a
K+ conductance that hyperpolarizes cells and lowers
their input resistance. These effects of GTPS were blocked in
KCl-filled cells. In view of the tight coupling between the G-protein
and activation of the GABAB-activated K+
conductance, the effect of Cl ions is likely to be
exerted either on the G-protein or the K+ channel
itself. We observed substantial effects of
Cli at concentrations that are
believed to exist during development in the CNS as well as during
pathological conditions, such as spreading depression. Thus, the
results we describe must be taken into consideration during such
physiological and pathological conditions as well as in experimental
studies of G-protein-modulated conductances.
Key words:
GABAB;
baclofen;
serotonin;
Ih;
spreading depression;
anions
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