title: Ca2+ nanodomain-mediated component of swelling-induced volume-sensitive outwardly rectifying anion current triggered by autocrine action of ATP in mouse astrocytes.
abstract: The volume-sensitive outwardly rectifying (VSOR) anion channel provides a major pathway for anion transport during cell volume regulation. It is typically activated in response to cell swelling, but how the channel senses the swelling remains unclear. Meanwhile, we recently found that in mouse astrocytes the channel is activated by an inflammatory chemical mediator, bradykinin, without cell swelling and that the activation is regulated via high concentration regions of intracellular Ca(2+) ([Ca(2+)](i)) in the immediate vicinity of open Ca(2+)-permeable channels, so-called Ca(2+) nanodomains. Here we investigated whether a similar mechanism is involved in the swelling-induced VSOR channel activation in the astrocytes. A hypotonic stimulus (25% reduction in osmolality) caused the [Ca(2+)](i) rises in the astrocytes, and the rises were abolished in the presence of an ATP-degrading enzyme, apyrase (10 U/ml). Application of ATP (100 μM) under isotonic conditions generated the current through VSOR channels via Ca(2+) nanodomains, as bradykinin does. The current induced by the hypotonic stimulus was suppressed by ~40% in the Ca(2+)-depleted condition where the ATP-induced VSOR current was totally prevented. Thus the swelling-induced VSOR channel activation in mouse astrocytes is partly regulated via Ca(2+) nanodomains, whose generation is triggered by an autocrine action of ATP.
authors.affiliation: Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi, Japan. tenpak@nips.ac.jp
authors.forename: Tenpei
authors.initials: T
authors.lastname: Akita
authors.forename: Sergei V
authors.initials: SV
authors.lastname: Fedorovich
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Okada
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D019898:Autocrine Communication; D002118:Calcium / Q000378:metabolism*; D048429:Cell Size; D018118:Chloride Channels / Q000378:metabolism / Q000502:physiology*; D007038:Hypotonic Solutions / Q000494:pharmacology; D051379:Mice; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism
chemical_list: D018118:Chloride Channels; D007038:Hypotonic Solutions; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D001081:Apyrase; D002118:Calcium