title: Functional identification of an outwardly rectifying pH- and anesthetic-sensitive leak K(+) conductance in hippocampal astrocytes.
abstract: 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.
authors.affiliation: Institute of Neuroscience and Brain Research Center, National Yang-Ming University, Section 2, Li-Nong St., Taipei, Taiwan.
authors.forename: Kuo-Chang
authors.initials: KC
authors.lastname: Chu
authors.forename: Cheng-Di
authors.initials: CD
authors.lastname: Chiu
authors.forename: Tsan-Ting
authors.initials: TT
authors.lastname: Hsu
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Hsieh
authors.forename: Yu-Yin
authors.initials: YY
authors.lastname: Huang
authors.forename: Cheng-Chang
authors.initials: CC
authors.lastname: Lien
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001464:Barium / Q000494:pharmacology; D002045:Bupivacaine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins; D018408:Patch-Clamp Techniques / Q000379:methods; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors / Q000502:physiology*; D011803:Quinine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D001464:Barium; D013779:Tetrodotoxin; C018564:dihydro-DIDS; D011803:Quinine; D007530:Isoflurane; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002045:Bupivacaine