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

Authors: Zhou, M  Xu, G  Xie, M  Zhang, X  Schools, GP  Ma, L  Kimelberg, HK  Chen, H 
Citation: Zhou M, etal., J Neurosci. 2009 Jul 1;29(26):8551-64. doi: 10.1523/JNEUROSCI.5784-08.2009.
Pubmed: (View Article at PubMed) PMID:19571146
DOI: Full-text: DOI:10.1523/JNEUROSCI.5784-08.2009

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 (K(2P)) 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 P(Cs)/P(K) permeability, 0.43, 0.10, and 0.05, respectively. Second, quinine, which potently inhibited TWIK-1 (IC(50) = 85 microm) and TREK-1 (IC(50) = 41 microm) currents, also inhibited astrocytic passive conductance by 58% at a concentration of 200 microm. 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 Ba(2+), and extracellular Ba(2+) blocked TWIK-1 channels at an IC(50) of 960 microm 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 K(2P) 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.

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RGD ID: 9831119
Created: 2015-02-25
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Last Modified: 2015-02-25
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.