TY - JOUR T1 - TWIK-1 and TREK-1 Are Potassium Channels Contributing Significantly to Astrocyte Passive Conductance in Rat Hippocampal Slices JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8551 LP - 8564 DO - 10.1523/JNEUROSCI.5784-08.2009 VL - 29 IS - 26 AU - Min Zhou AU - Guangjin Xu AU - Minjie Xie AU - Xuexin Zhang AU - Gary P. Schools AU - Liqun Ma AU - Harold K. Kimelberg AU - Haijun Chen Y1 - 2009/07/01 UR - http://www.jneurosci.org/content/29/26/8551.abstract N2 - 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. ER -