Characterization of the voltage-dependent properties of a volume-sensitive anion conductance

Outwardly rectified, swelling-activated anion conductances have been described in numerous cell types. The major functional variable observed amongst these conductances is the extent and rate of depolarization-induced inactivation. In general, the conductances can be divided into two broad classes, those that show rapid inactivation in response to strong depolarization and those that show little or no voltage dependence. The swelling-activated anion conductance in rat C6 glioma cells is inactivated nearly completely by membrane depolarization above +90 mV and reactivated by membrane hyperpolarization. The kinetics of inactivation and reactivation are fit by single and double exponentials, respectively. Voltage-dependent behavior is well described by a simple linear kinetic model in which the channel exists in an open or one of three inactivated states. pH-induced changes in voltage-dependent gating suggest that the voltage sensor contains critical basic amino acid residues. Extracellular ATP blocks the channel in a voltage-dependent manner. The block is sensitive to the direction of net Cl- movement and increases open channel noise indicating that ATP interacts with the channel pore. Blockage of the channel with ATP dramatically slows depolarization-induced inactivation.