期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 28, 期 3, 页码 456-467出版社
SAGE PUBLICATIONS INC
DOI: 10.1038/sj.jcbfm.9600545
关键词
acute hippocampal slices; astrocytes; membrane potential; oxygen-glucose deprivation; patch clamp
资金
- NINDS NIH HHS [R01 NS 35205] Funding Source: Medline
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 similar to 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, similar to 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 Vm change. The Vm 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 Vm hyperpolarization relative to the control Vm 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.
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