Changes in Astroglial K(+) upon Brief Periods of Energy Deprivation in the Mouse Neocortex

Malfunction of astrocytic K(+) regulation contributes to the breakdown of extracellular K(+) homeostasis during ischemia and spreading depolarization events. Studying astroglial K(+) changes is, however, hampered by a lack of suitable techniques. Here, we combined results from fluorescence imaging, ion-selective microelectrodes, and patch-clamp recordings in murine neocortical slices with the calculation of astrocytic [K(+)]. Brief chemical ischemia caused a reversible ATP reduction and a transient depolarization of astrocytes. Moreover, astrocytic [Na(+)] increased by 24 mM and extracellular [Na(+)] decreased. Extracellular [K(+)] increased, followed by an undershoot during recovery. Feeding these data into the Goldman–Hodgkin–Katz equation revealed a baseline astroglial [K(+)] of 146 mM, an initial K(+) loss by 43 mM upon chemical ischemia, and a transient K(+) overshoot of 16 mM during recovery. It also disclosed a biphasic mismatch in astrocytic Na(+)/K(+) balance, which was initially ameliorated, but later aggravated by accompanying changes in pH and bicarbonate, respectively. Altogether, our study predicts a loss of K(+) from astrocytes upon chemical ischemia followed by a net gain. The overshooting K(+) uptake will promote low extracellular K(+) during recovery, likely exerting a neuroprotective effect. The resulting late cation/anion imbalance requires additional efflux of cations and/or influx of anions, the latter eventually driving delayed astrocyte swelling.