title: Oxygen and glucose deprivation-induced changes in astrocyte membrane potential and their underlying mechanisms in acute rat hippocampal slices.
abstract: Accumulating evidence indicates a significant astrocytic involvement in cerebral ischemia neuropathology, but little is known about the immediate astrocytic responses to ischemia insults in terms of electrophysiology and their pathologic implications. We show that astrocytes in acute rat hippocampal slices responded reversibly to more than 30 mins oxygen and glucose deprivation (OGD) treatment with depolarized membrane potentials (V(m)) in whole-cell current clamp recording. This depolarization was multiphasic, showing an initial approximately 11 mins small-amplitude depolarization plateau, followed by a 6-mins accelerated depolarization, and then a second plateau. Oxygen and glucose deprivation-induced astrocyte V(m) depolarization was only marginally inhibited, approximately 10%, by inhibition of ionotropic glutamate, gamma-aminobutyric acid, purinergic receptors, and glutamate transporters presumed to be present on astrocytes in situ, suggesting increase in extracellular [K(+)] was primarily responsible for the astrocytic V(m) change. The V(m) depolarization was five-fold greater when glycolysis was inhibited by iodoacetate in a short 8 mins OGD treatment, suggesting glycolytic ATP is critical in maintaining extracellular K(+) homeostasis in the early phase of OGD. Addition of oxidative metabolism inhibitors had much less effect. Cessation of OGD was always followed by a rapid and transient 9 mV astrocyte V(m) hyperpolarization relative to the control V(m) that was inhibited by ouabain, indicating a reactively enhanced Na(+)/K(+)-ATPase activity in post-OGD reperfusion. Altogether, hippocampal astrocytes appear to be electrophysiologically more resistant to acute ischemia insults as compared with neurons, and this should allow astrocytes to rescue endangered neurons in the face of acute ischemia insults via their various homeostatic functions.
authors: Department of Neural and Vascular Biology, Ordway Research Institute, Albany, NY 12208, USA.
authors: Minjie
authors: M
authors: Xie
authors: Wei
authors: W
authors: Wang
authors: Harold K
authors: HK
authors: Kimelberg
authors: Min
authors: M
authors: Zhou
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology*; D004594:Electrophysiology; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000473:pathology*; D002534:Hypoxia, Brain / Q000473:pathology*; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology; D008564:Membrane Potentials; D009474:Neurons / Q000473:pathology; D010100:Oxygen / Q000097:blood; D051381:Rats
chemical_list: D005947:Glucose; D010100:Oxygen