Activity-dependent changes in transporter and potassium currents in hippocampal astrocytes

Abstract

Astrocytes are involved in maintenance of synaptic microenvironment by glutamate uptake and K⁺ clearance. These processes are associated with net charge transfer across the membrane and therefore can be recorded as glutamate transporter (I_GluT) and K⁺ (I_K) currents. It has been previously shown that the blockade of I_K with BaCl₂ enhances the I_GluT. Here we show that activity-dependent facilitation (5 stimuli at 50Hz) of I_GluT was not significantly different in BaCl₂ compared to facilitation of I_GluT isolated by post-hoc subtraction of I_K. Nevertheless, BaCl₂ abolished the activity-dependent prolongation of τ_decay, which was observed for I_GluT isolated by post-hoc subtraction of I_K. This finding suggests that activity-dependent accumulation of extracellular K⁺ ([K⁺]_o) causes astrocytic depolarization, which is responsible for the increase in τ_decay of I_GluT. The blockade of inward rectifying K⁺ channels (K_ir) with BaCl₂ makes astrocytic membrane potential insensitive to [K⁺]_o elevation and thus abolishes this increase. Blockade of I_GluT with glutamate transporter blocker, DL-threo-β-benzyloxyaspartic acid (TBOA) did not significantly affect the amplitude of I_K but decreased its τ_decay. However, activity dependent facilitations of both amplitude and τ_decay of I_K were larger in TBOA, than in the control conditions. We suggest that activity-dependent accumulation of extracellular glutamate can enhance release of K⁺. Thus activity-dependent changes in [K⁺]_o can affect glutamate dwell-time in the synaptic cleft, and vice versa, extracellular glutamate accumulation can affect [K⁺]_o time-course. Our finding is important for understanding of the astrocytic mechanisms in glutamate excitotoxicity and in diseases related to disruption of K⁺ homeostasis (e.g. stroke, migraine, and epilepsy).

Keywords: Astrocytes; Glutamate uptake; Potassium.