Two-pore-domain potassium channels contribute to neuronal potassium release and glial potassium buffering in the rat hippocampus.
Two-pore-domain potassium (K2P) channels have been suggested to be involved in neuronal K+ release and glial K+ uptake. We studied effects of the K2P channel blockers quinine (200 or 500 microM), quinidine (500 microM), and bupivacaine (200 microM) on stimulus-induced and iontophoretically induced transient increases of the extracellular potassium concentration ([K+]o) in area CA1 of rat hippocampal slices, always in presence of AMPA/kainate and NMDA receptor antagonists. Increases in [K+]o evoked by repetitive alvear stimulation (20 Hz) were blocked by quinine and quinidine but amplitudes of population spikes were only modestly reduced. Bupivacaine suppressed both rises in [K+]o and population spikes. In contrast, iontophoretically induced rises in [K+]o were moderately augmented by quinine and quinidine while bupivacaine had no effect. Barium at concentrations of 2 mM which should block both potassium inward rectifier (Kir) and some K2P channels doubled iontophoretically induced rises in [K+]o also in presence of quinine, quinidine, and bupivacaine. The data suggest that quinine/quinidine-sensitive K2P channels mediate K+ release from neurons and possibly contribute to glial K+ buffering.
Päsler
Dennis
D
Institute for Neurophysiology, Charité - Medical University of Berlin, Tucholskystr. 2, 10117 Berlin, Germany.
Gabriel
Siegrun
S
Heinemann
Uwe
U
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002045:Bupivacaine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D011188:Potassium / Q000494:pharmacology / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D011803:Quinine / Q000494:pharmacology; D051381:Rats
D018712:Analgesics, Non-Narcotic; D018691:Excitatory Amino Acid Antagonists; D015221:Potassium Channels; D001464:Barium; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D011803:Quinine; D011188:Potassium; D002045:Bupivacaine