Impact of global cerebral ischemia on K+ channel expression and membrane properties of glial cells in the rat hippocampus
Abstract
Astrocytes and NG2 glia respond to CNS injury by the formation of a glial scar. Since the changes in K+ currents in astrocytes and NG2 glia that accompany glial scar formation might influence tissue outcome by altering K+ ion homeostasis, we aimed to characterize the changes in K+ currents in hippocampal astrocytes and NG2 glia during an extended time window of reperfusion after ischemic injury.
Global cerebral ischemia was induced in adult rats by bilateral, 15-min common carotid artery occlusion combined with low-pressure oxygen ventilation. Using the patch-clamp technique, we investigated the membrane properties of hippocampal astrocytes and NG2 glia in situ 2 hours, 6 hours, 1 day, 3 days, 7 days or 5 weeks after ischemia.
Astrocytes in the CA1 region of the hippocampus progressively depolarized starting 3 days after ischemia, which coincided with decreased Kir4.1 protein expression in the gliotic tissue. Other K+ channels described previously in astrocytes, such as Kir2.1, Kir5.1 and TREK1, did not show any changes in their protein content in the hippocampus after ischemia: however, their expression switched from neurons to reactive astrocytes, as visualized by immunohistochemistry.
NG2 glia displayed increased input resistance, decreased membrane capacitance, increased delayed outwardly rectifying and A-type K+ currents and decreased inward K+ currents 3 days after ischemia, accompanied by their proliferation. Our results show that the membrane properties of astrocytes after ischemia undergo complex alterations, which might profoundly influence the maintenance of K+ homeostasis in the damaged tissue, while NG2 glia display membrane currents typical of proliferating cells.