Ca2+ store-dependent potentiation of Ca2+-activated non-selective cation channels in rat hippocampal neurones in vitro

Authors

  • L. Donald Partridge,

    Corresponding author
    1. Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87133, USA
    • Corresponding author
      L. D. Partridge: Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87133, USA. Email: dpartridge@salud.unm.edu

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  • C. Fernando Valenzuela

    1. Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87133, USA
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Abstract

  • 1Potentiation 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.
  • 2The CAN channel-dependent depolarization (ΔVCAN) was potentiated when [Ca2+]i was increased in neurones impaled with Ca2+-containing microelectrodes.
  • 3Fura-2 measurements revealed a biphasic increase in [Ca2+]i when 200 μm ACPD was bath applied to cultured hippocampal neurones. This increase was greatly attenuated in the presence of Cd2+.
  • 4Thapsigargin (1 μm) caused marked potentiation of ΔVCAN in CA1 neurones in the slices and of the CAN current (ICAN) measured in whole cell-clamped cultured hippocampal neurones.
  • 5Ryanodine (20 μm) also led to a potentiation of ΔVCAN while neurones pretreated with 100 μm dantrolene failed to show potentiation of ΔVCAN when impaled with Ca2+-containing microelectrodes.
  • 6The mitochondrial oxidative phosphorylation uncoupler carbonyl cyanide m-chlorophenyl hydrazone (2 μm) also caused a potentiation of ΔVCAN.
  • 7CAN 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.

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