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      Genetic Deletion of TREK-1 or TWIK-1/TREK-1 Potassium Channels does not Alter the Basic Electrophysiological Properties of Mature Hippocampal Astrocytes In Situ


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          We have recently shown that a linear current-to-voltage (I-V) relationship of membrane conductance (passive conductance) reflects the intrinsic property of K + channels in mature astrocytes. While passive conductance is known to underpin a highly negative and stable membrane potential ( V M) essential for the basic homeostatic function of astrocytes, a complete repertoire of the involved K + channels remains elusive. TREK-1 two-pore domain K + channel (K 2P) is highly expressed in astrocytes, and covalent association of TREK-1 with TWIK-1, another highly expressed astrocytic K 2P, has been reported as a mechanism underlying the trafficking of heterodimer TWIK-1/TREK-1 channel to the membrane and contributing to astrocyte passive conductance. To decipher the individual contribution of TREK-1 and address whether the appearance of passive conductance is conditional to the co-expression of TWIK-1/TREK-1 in astrocytes, TREK-1 single and TWIK-1/TREK-1 double gene knockout mice were used in the present study. The relative quantity of mRNA encoding other astrocyte K + channels, such as K ir4.1, K ir5.1, and TREK-2, was not altered in these gene knockout mice. Whole-cell recording from hippocampal astrocytes in situ revealed no detectable changes in astrocyte passive conductance, V M, or membrane input resistance ( R in) in either kind of gene knockout mouse. Additionally, TREK-1 proteins were mainly located in the intracellular compartments of the hippocampus. Altogether, genetic deletion of TREK-1 alone or together with TWIK-1 produced no obvious alteration in the basic electrophysiological properties of hippocampal astrocytes. Thus, future research focusing on other K + channels may shed light on this long-standing and important question in astrocyte physiology.

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          Astrocyte control of synaptic transmission and neurovascular coupling.

          From a structural perspective, the predominant glial cell of the central nervous system, the astrocyte, is positioned to regulate synaptic transmission and neurovascular coupling: the processes of one astrocyte contact tens of thousands of synapses, while other processes of the same cell form endfeet on capillaries and arterioles. The application of subcellular imaging of Ca2+ signaling to astrocytes now provides functional data to support this structural notion. Astrocytes express receptors for many neurotransmitters, and their activation leads to oscillations in internal Ca2+. These oscillations induce the accumulation of arachidonic acid and the release of the chemical transmitters glutamate, d-serine, and ATP. Ca2+ oscillations in astrocytic endfeet can control cerebral microcirculation through the arachidonic acid metabolites prostaglandin E2 and epoxyeicosatrienoic acids that induce arteriole dilation, and 20-HETE that induces arteriole constriction. In addition to actions on the vasculature, the release of chemical transmitters from astrocytes regulates neuronal function. Astrocyte-derived glutamate, which preferentially acts on extrasynaptic receptors, can promote neuronal synchrony, enhance neuronal excitability, and modulate synaptic transmission. Astrocyte-derived d-serine, by acting on the glycine-binding site of the N-methyl-d-aspartate receptor, can modulate synaptic plasticity. Astrocyte-derived ATP, which is hydrolyzed to adenosine in the extracellular space, has inhibitory actions and mediates synaptic cross-talk underlying heterosynaptic depression. Now that we appreciate this range of actions of astrocytic signaling, some of the immediate challenges are to determine how the astrocyte regulates neuronal integration and how both excitatory (glutamate) and inhibitory signals (adenosine) provided by the same glial cell act in concert to regulate neuronal function.
            • Record: found
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            New roles for astrocytes: redefining the functional architecture of the brain.

            Astrocytes have traditionally been considered ancillary, satellite cells of the nervous system. However, work over the past decade has revealed that they interact with the vasculature to form a gliovascular network that might organize not only the structural architecture of the brain but also its communication pathways, activation, thresholds and plasticity. The net effect is that astroglia demarcate gray matter regions, both cortical and subcortical, into functional compartments whose internal activation thresholds and external outputs are regulated by single glial cells. The array of these astrocyte-delimited microdomains along the capillary microvasculature allows the formation of higher-order gliovascular units, which serve to match local neural activity and blood flow while regulating neuronal firing thresholds through coordinative glial signaling. By these means, astrocytes might establish the functional as well as the structural architecture of the adult brain.
              • Record: found
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              Molecular background of leak K+ currents: two-pore domain potassium channels.

              Two-pore domain K(+) (K(2P)) channels give rise to leak (also called background) K(+) currents. The well-known role of background K(+) currents is to stabilize the negative resting membrane potential and counterbalance depolarization. However, it has become apparent in the past decade (during the detailed examination of the cloned and corresponding native K(2P) channel types) that this primary hyperpolarizing action is not performed passively. The K(2P) channels are regulated by a wide variety of voltage-independent factors. Basic physicochemical parameters (e.g., pH, temperature, membrane stretch) and also several intracellular signaling pathways substantially and specifically modulate the different members of the six K(2P) channel subfamilies (TWIK, TREK, TASK, TALK, THIK, and TRESK). The deep implication in diverse physiological processes, the circumscribed expression pattern of the different channels, and the interesting pharmacological profile brought the K(2P) channel family into the spotlight. In this review, we focus on the physiological roles of K(2P) channels in the most extensively investigated cell types, with special emphasis on the molecular mechanisms of channel regulation.

                Author and article information

                Front Cell Neurosci
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Media S.A.
                03 February 2016
                : 10
                : 13
                [1] 1Department of Neuroscience, The Ohio State University Wexner Medical Center Columbus, OH, USA
                [2] 2Department of Neurology, The First Affiliated Hospital of Nanjing Medical University Nanjing, China
                [3] 3Department of Neurology, Meitan General Hospital Xibahe Nanli, Beijing, China
                [4] 4Department of Physiology, Institute of Brain Research, School of Basic Medicine, Huazhong University of Science and Technology Wuhan, China
                [5] 5Department of Biological Science, University at Albany, State University of New York Albany, NY, USA
                [6] 6Department of Anesthesiology, Baylor College of Medicine Houston, TX, USA
                Author notes

                Edited by: Marco Martina, Northwestern University, USA

                Reviewed by: Douglas A. Bayliss, University of Virginia, USA; Julien Dine, Max Planck Institut of Psychiatry, Germany

                *Correspondence: Min Zhou zhou.787@ 123456osu.edu
                Copyright © 2016 Du, Kiyoshi, Wang, Wang, Ma, Alford, Zhong, Wan, Chen, Lloyd, Bryan and Zhou.

                and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                : 01 September 2015
                : 14 January 2016
                Page count
                Figures: 7, Tables: 1, Equations: 2, References: 70, Pages: 13, Words: 9825
                Funded by: National Institute of Neurological Disorders and Stroke 10.13039/100000065
                Award ID: RO1NS062784
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81400973
                Original Research

                astrocytes,trek-1 potassium channel,passive membrane conductance,patch-clamp recording,hippocampus


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