Intracellular chloride modulates A‐type potassium currents in astrocytes

Publisher Website
Google Scholar
Abstract
Application of the GABAA 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 (V1/2, −68 to −57 mV) and activation (V1/2, −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.