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Intracellular chloride modulates A‐type potassium currents in astrocytes
Author(s) -
Bekar Lane K.,
Walz Wolfgang
Publication year - 2002
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10096
Subject(s) - muscimol , pipette , biophysics , intracellular , reversal potential , gramicidin , depolarization , patch clamp , kinetics , agonist , chemistry , biology , biochemistry , receptor , membrane , physics , quantum mechanics
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.