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The mechanism of neuroprotection by positive modulation of Ca2+-activated K+ channels of cerebellar neurons in primary culture

  • Yu. D. Stepanenko
  • T. V. Karelina
  • D. A. Sibarov
  • P. A. Abushik
  • S. M. Antonov
Short Communication
  • 27 Downloads

Abstract

Here we show that positive modulators (CyPPA and NS309) of Ca2+-activated K+ channels of small (SK) and intermediate (IK) conductances in cerebellar neurons decrease glutamate-evoked Ca2+ entry into neurons independently on the presence of Mg2+ in extracellular media. An analysis of neuronal viability after long-term (240 min) glutamate treatments demonstrated neuroprotective action of CyPPA and NS309. Extracellular Mg2+ did not protect neurons from apoptosis during prolonged treatment with glutamate. Activation of SK and IK channels results in local membrane hyperpolarization, which enhances Mg2+ block of NMDA receptors and reduces activation of voltage-dependent Ca2+ channels, which can explain neuroprotection caused by CyPPA or NS309. The obtained results reveal an important role Ca2+-activated K+ channels of small and intermediate conductance in the regulation of Ca2+ entry into cerebellar neurons via NMDA receptors and voltage-gated Ca2+ channels.

Keywords

primary culture neurons cerebellum SK channels calcium 

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Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  • Yu. D. Stepanenko
    • 1
  • T. V. Karelina
    • 1
  • D. A. Sibarov
    • 1
  • P. A. Abushik
    • 1
  • S. M. Antonov
    • 1
  1. 1.Sechenov Institute of Evolutionary Physiology and BiochemistryRussian Academy of SciencesSt. PetersburgRussia

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