Abstract
Application of the GABA~A~ receptor agonist muscimol to astrocytes in situ or in vitro results in a receptor‐mediated Cl^−^ current with a concomitant block of outward K^+^ currents. The effect on K^+^ current is largely selective for the inactivating A‐type current. Parallel experiments with various Cl^−^ pipette concentrations show a significant reduction in A‐type current under low Cl^−^ conditions with minimal effect on delayed current. In addition, lower Cl^−^ conditions caused a depolarizing shift of steady‐state inactivation (V~1/2~, −68 to −57 mV) and activation (V~1/2~, −5.8 to 34 mV) kinetics of A‐type current only. Cl^−^ had no effect on the time course of inactivation or reactivation kinetics, suggesting the Cl^−^‐mediated effect is largely on activation kinetics, indirectly affecting steady‐state inactivation. Muscimol application to astrocytes under perforated patch control (gramicidin) displayed a similar block of A‐type current to that of conventional whole cell patch at 40 or 20 mM pipette Cl^−^ concentrations. With barium application under perforated patch conditions, the study of muscimol‐mediated Cl^−^ current in isolation of the effect on K^+^ currents was possible. This allowed estimation of intracellular Cl^−^ concentration from receptor current reversal information. The average intracellular Cl^−^ concentration was found to be 29 ± 3.2 mM. The effect on activation kinetics and lack of effect on time course of inactivation or reactivation suggest that intracellular anion concentrations have an effect on the K^+^ channel voltage sensor region. Cl^−^ may modulate K^+^ currents by altering membrane field potentials surrounding K^+^ channel proteins. GLIA 39:207–216, 2002. © 2002 Wiley‐Liss, Inc.