Ra. Lenz et al., HIGH INTRACELLULAR CL- CONCENTRATIONS DEPRESS G-PROTEIN-MODULATED IONIC CONDUCTANCES, The Journal of neuroscience, 17(16), 1997, pp. 6133-6141
Numerous G-protein-modulated ionic conductances are present in central
neurons and play major roles in regulating neuronal excitability. Acc
ordingly, endogenous factors that alter the operation of these conduct
ances may have profound effects on neuronal function. We now report th
at several G-protein-modulated ionic conductances in hippocampal neuro
ns are very much altered when Cl- is the predominant anion in the reco
rding electrode. We used both sharp-electrode and whole-cell technique
s in rat hippocampal slices to determine whether hippocampal CA1 pyram
idal cell properties are altered by KCl-filled, as compared with KCH3S
O3 or K-gluconate-filled, electrodes. We studied the effects of the an
ions on synaptically evoked GABA(B) responses and baclofen-and seroton
in-induced currents as well as on a voltage-activated cation current,
I-h. High intracellular concentrations of chloride ([Cl-](i)) depresse
d all the responses without altering resting cell properties. Intermed
iate [Cl-](i) reduced baclofen-induced currents rents as well as I-h i
n a dose-dependent manner. In KCH3SO3-filled cells, equimolar substitu
tion of GTP gamma S for Tris-GTP results in activation of a K+ conduct
ance that hyperpolarizes cells and lowers their input resistance. Thes
e effects of GTP gamma S were blocked in KCl-filled cells. In view of
the tight coupling between the G-protein and activation of the GABA(B)
-activated K+ conductance, the effect of Cl- ions is likely to be exer
ted either on the G-protein or the K+ channel itself. We observed subs
tantial effects of Cl-i(-) at concentrations that are believed to exis
t during development in the CNS as well as during pathological conditi
ons, 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.