Dissipation of transmembrane potassium gradient is the main cause of cerebral ischemia-induced depolarization in astrocytes and neurons.

Autor: Du Y; Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA., Wang W; Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, China., Lutton AD; Trace Element Research Laboratory, The Ohio State University, Columbus, OH 43210, USA., Kiyoshi CM; Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA., Ma B; Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA., Taylor AT; Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA., Olesik JW; Trace Element Research Laboratory, The Ohio State University, Columbus, OH 43210, USA., McTigue DM; Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA., Askwith CC; Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA., Zhou M; Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. Electronic address: zhou.787@osu.edu.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2018 May; Vol. 303, pp. 1-11. Date of Electronic Publication: 2018 Feb 03.
DOI: 10.1016/j.expneurol.2018.01.019
Abstrakt: Membrane potential (V M ) depolarization occurs immediately following cerebral ischemia and is devastating for the astrocyte homeostasis and neuronal signaling. Previously, an excessive release of extracellular K + and glutamate has been shown to underlie an ischemia-induced V M depolarization. Ischemic insults should impair membrane ion channels and disrupt the physiological ion gradients. However, their respective contribution to ischemia-induced neuronal and glial depolarization and loss of neuronal excitability are unanswered questions. A short-term oxygen-glucose deprivation (OGD) was used for the purpose of examining the acute effect of ischemic conditions on ion channel activity and physiological K + gradient in neurons and glial cells. We show that a 30 min OGD treatment exerted no measurable damage to the function of membrane ion channels in neurons, astrocytes, and NG2 glia. As a result of the resilience of membrane ion channels, neuronal spikes last twice as long as our previously reported 15 min time window. In the electrophysiological analysis, a 30 min OGD-induced dissipation of transmembrane K + gradient contributed differently in brain cell depolarization: severe in astrocytes and neurons, and undetectable in NG2 glia. The discrete cellular responses to OGD corresponded to a total loss of 69% of the intracellular K + contents in hippocampal slices as measured by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). A major brain cell depolarization mechanism identified here is important for our understanding of cerebral ischemia pathology. Additionally, further understanding of the resilient response of NG2 glia to ischemia-induced intracellular K + loss and depolarization should facilitate the development of future stroke therapy.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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