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

Int J Mol Sci. 2022 Apr 27;23(9):4836. doi: 10.3390/ijms23094836.


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.

Keywords: ATeam; astrocyte; extracellular space; imaging; ion-sensitive microelectrodes; ischemia; pH; patch-clamp; potassium; sodium.

MeSH terms

  • Animals
  • Astrocytes* / metabolism
  • Homeostasis / physiology
  • Ischemia / metabolism
  • Mice
  • Neocortex* / metabolism
  • Potassium / metabolism
  • Sodium / metabolism


  • Sodium
  • Potassium