Intracellular [Cl−] modulates synchronous electrical activity in rat neocortical neurons in culture by way of GABAergic inputs

The influence of GABAergic neurons on spontaneous electrical activities of neocortical neurons in culture, which was estimated to be about 9.5% of the total neurons by immunohistochemistry, was examined using dual whole-cell recording. Synchronized depolarization or hyperpolarization was observed in recorded neurons with pipettes containing low [Cl(-)] solution, while synchronized bursting of action potentials (APs) was observed with pipettes containing high [Cl(-)] solution. Spontaneous currents (SCs) were synchronous in all pairs tested with either pipettes containing low or high [Cl(-)] solution and spontaneous outward currents (SOCs) observed at around -30 mV were sensitive to the GABA-A receptor antagonist, bicuculline. Their reversal potential (V(rev)) was linearly related to the logarithm of Cl(-) activity in the pipette (-56.9 mV/decade). The intracellular chloride concentration was estimated from the V(rev) of SCs with gramicidin perforated-patch recordings and was between 5.9 and 28.1 mM (mean: 13.0 mM). These results suggest that GABA depolarized some neurons and hyperpolarized others, depending on the E(Cl). Bicuculline decreased the frequency of periodic depolarized potentials and increased their amplitudes. However, perfusion with low [Cl(-)] bath solution did not decrease the frequency. Our data indicate that recurrent subthreshold electrical activities by GABAergic inputs along with glutamatergic inputs take part in deterring synchronized bursting and that intracellular [Cl(-)] can modulate this bursting.