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Functional identification of an outwardly rectifying pH‐ and anesthetic‐sensitive leak K + conductance in hippocampal astrocytes
Author(s) -
Chu KuoChang,
Chiu ChengDi,
Hsu TsanTing,
Hsieh YuMing,
Huang YuYin,
Lien ChengChang
Publication year - 2010
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2010.07323.x
Subject(s) - chemistry , conductance , isoflurane , biophysics , tetrodotoxin , tetraethylammonium , membrane potential , electrophysiology , patch clamp , reversal potential , channel blocker , neuroscience , anesthesia , biochemistry , medicine , biology , receptor , potassium , mathematics , organic chemistry , combinatorics , calcium
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 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 Ba 2+ 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.