Functional identification of an outwardly rectifying pH- and anesthetic-sensitive leak K+ conductance in hippocampal astrocytes
Functional identification of an outwardly rectifying pH- and anesthetic-sensitive leak K+ conductance in hippocampal astrocytes
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DOI：
10.1111/j.1460-9568.2010.07323.x
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发表时间：
2010-09-01
影响因子：
3.4
通讯作者：
Lien, Cheng-Chang
中科院分区：
文献类型：
--
作者：
Chu, Kuo-Chang;Chiu, Cheng-Di;Lien, Cheng-Chang
Astrocytes function as spatial K+ buffers by expressing a rich repertoire of K+ channels. Earlier studies suggest that acid-sensitive tandem-pore K+ channels, mainly TWIK-related acid-sensitive K+ (TASK) channels, mediate part of the passive astroglial membrane conductance. Here, using a combination of electrophysiology and pharmacology, we investigated the presence of TASK-like conductance in hippocampal astrocytes of rat brain slices. Extracellular pH shifts to below 7.4 (or above 7.4) induced a prominent inward (or outward) current in astrocytes in the presence of tetrodotoxin, a Na+ channel blocker, and 4,4'-diisothiocyanatostilbene-2,2'- disulfonate, a Na+ - HCO(3)(-)co-transporter blocker. The pH-sensitive current was insensitive to quinine, a potent blocker of tandem-pore K+ channels including TWIK-1 and TREK-1 channels. Voltage-clamp analysis revealed that the pH-sensitive current exhibited weak outward rectification with a reversal potential of) -112 mV, close to the Nernst equilibrium potential for K+. Furthermore, the current-voltage relationship was well fitted with the Goldman-Hodgkin-Katz current equation for the classical open-rectifier 'leak' K+ channel. The pH-sensitive K+ current was potentiated by TASK channel modulators such as the volatile anesthetic isoflurane but depressed by the local anesthetic bupivacaine. However, unlike TASK channels, the pH-sensitive current was insensitive to Ba2+ and quinine. Thus, the molecular identity of the pH-sensitive leak K+ channel is unlikely to be attributable to TASK channels. Taken together, our results suggest a novel yet unknown leak K+ channel underlying the pH-and anesthetic-sensitive background conductance in hippocampal astrocytes.
