TWIK-1 and TREK-1 are potassium channels contributing significantly to astrocyte passive conductance in rat hippocampal slices

Min Zhou, Guangjin Xu, Minjie Xie, Xuexin Zhang, Gary P. Schools, Liqun Ma, Harold K. Kimelberg, Haijun Chen

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115 Scopus citations

Abstract

Expression of a linear current-voltage (I-V) relationship (passive) K + membrane conductance is a hallmark of mature hippocampal astrocytes. However, the molecular identifications of the K+ channels underlying this passive conductance remain unknown. We provide the following evidence supporting significant contribution of the two-pore domain K + channel (K2P) isoforms, TWIK-1 and TREK-1, to this conductance. First, both passive astrocytes and the cloned rat TWIK-1 and TREK-1 channels expressed in CHO cells conduct significant amounts of Cs+ currents, but vary in their relative PCs/PK permeability, 0.43, 0.10, and 0.05, respectively. Second, quinine, which potently inhibited TWIK-1 (IC50=85 μM) and TREK-1 (IC50=41 μM) currents, also inhibited astrocytic passive conductance by 58% at a concentration of 200 μM. Third, a moderate sensitivity of passive conductance to low extracellular pH (6.0) supports a combined expression of acid-insensitive TREK-1, and to a lesser extent, acid-sensitive TWIK-1. Fourth, the astrocyte passive conductance showed low sensitivity to extracellular Ba2+, and extracellular Ba2+ blocked TWIK-1 channels at an IC50 of 960 μM and had no effect on TREK-1 channels. Finally, an immunocytochemical study showed colocalization of TWIK-1 and TREK-1 proteins with the astrocytic markers GLAST and GFAP in rat hippocampal stratum radiatum. In contrast, another K2P isoform TASK-1 was mainly colocalized with the neuronal marker NeuN in hippocampal pyramidal neurons and was expressed at a much lower level in astrocytes. These results support TWIK-1 and TREK-1 as being the major components of the long-sought K+ channels underlying the passive conductance of mature hippocampal astrocytes.

Original languageEnglish (US)
Pages (from-to)8551-8564
Number of pages14
JournalJournal of Neuroscience
Volume29
Issue number26
DOIs
StatePublished - Jul 1 2009

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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