Ca2+ store-dependent potentiation of Ca2+-activated non-selective cation channels in rat hippocampal neurones in vitro.
1. Potentiation of calcium-activated non-selective cation (CAN) channels was studied in rat hippocampal neurones. CAN channels were activated by IP3-dependent Ca2+ release following metabotropic glutamate receptor (mGluR) stimulation either by Schaffer collateral input to CA1 neurones in brain slices in which ionotropic glutamate and GABAA receptors, K+ channels, and the Na+-Ca2+ exchanger were blocked or by application of the mGluR antagonist ACPD in cultured hippocampal neurones. 2. The CAN channel-dependent depolarization (DeltaVCAN) was potentiated when [Ca2+]i was increased in neurones impaled with Ca2+-containing microelectrodes. 3. Fura-2 measurements revealed a biphasic increase in [Ca2+]i when 200 microM ACPD was bath applied to cultured hippocampal neurones. This increase was greatly attenuated in the presence of Cd2+. 4. Thapsigargin (1 microM) caused marked potentiation of DeltaVCAN in CA1 neurones in the slices and of the CAN current (ICAN) measured in whole cell-clamped cultured hippocampal neurones. 5. Ryanodine (20 microM) also led to a potentiation of DeltaVCAN while neurones pretreated with 100 microM dantrolene failed to show potentiation of DeltaVCAN when impaled with Ca2+-containing microelectrodes. 6. The mitochondrial oxidative phosphorylation uncoupler carbonyl cyanide m-chlorophenyl hydrazone (2 microM) also caused a potentiation of DeltaVCAN. 7. CAN channels are subject to considerable potentiation following an increase in [Ca2+]i due to Ca2+ release from IP3-sensitive, Ca2+-sensitive, or mitochondrial Ca2+ stores. This ICAN potentiation may play a crucial role in the 'amplification' phase of excitotoxicity.
Partridge
L D
LD
Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque 87133, USA. dpartridge@salud.unm.edu
Valenzuela
C F
CF
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology*; D002412:Cations / Q000378:metabolism; D002478:Cells, Cultured; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists
D002412:Cations; D007473:Ion Channels; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium