title: pH-Sensitive K(+) Currents and Properties of K2P Channels in Murine Hippocampal Astrocytes.
abstract: Based on their intimate spatial association with synapses and the capillary, astrocytes are critically involved in the control of ion, transmitter, and energy homeostasis as well as regulation of the cerebral blood flow. Under pathophysiological conditions, dysfunctional astrocytes can no longer assure homeostatic control although the underlying mechanisms are poorly understood. Specifically, neurological diseases are often accompanied by acidification of the extracellular space, but the properties of astrocytes in such an acidic environment are still a matter of debate. To meet the homeostatic requirements, astrocytes are equipped with intercellular gap junctions, inwardly rectifying K(+) (Kir) channels, and two-pore domain K(+) (K2P) channels. One goal of the present study was to overview current knowledge about astrocyte K(+) channel function during acidosis. In addition, we combined functional and molecular analyses to clarify how low pH affects K(+) channel function in astrocytes freshly isolated from the developing mouse hippocampus. Extracellular acidification led to a decrease of K(+) currents in astrocytes, probably due to modulation of Kir4.1 channels. After blocking Kir4.1 channels, low pH enhanced K(+) current amplitudes. This current activation was mimicked by modulators of TREK-1 channels, which belong to the K2P channels family. We found no evidence for the presence of acid-sensitive ion channels and transient receptor potential vanilloid receptors in hippocampal astrocytes. In conclusion, the assembly of astrocytic K(+) channels allows tolerating short, transient acidification, and glial Kir4.1 and K2P channels can be considered promising new targets in brain diseases accompanied by pH shifts.
authors.affiliation: Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Weller
authors.affiliation: Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany. Electronic address: christian.steinhaeuser@ukb.uni-bonn.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Steinhäuser
authors.affiliation: Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Seifert
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015221:Potassium Channels
keywords: Astrocyte; K(2)P; Kir4.1; TREK-1; TWIK-1; Two-pore domain potassium channel; pH