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Related Experiment Videos

Peroxynitrite affects Ca2+ influx through voltage-dependent calcium channels.

S Ohkuma1, M Katsura, A Higo

  • 1Department of Pharmacology, Kawasaki Medical School, Matsushima, Kurashiki, Japan. sohkuma@bcc.kawasaki-m.ac.jp

Journal of Neurochemistry
|February 24, 2001
PubMed
Summary

Peroxynitrite (OONO-) affects neuronal calcium channels, increasing influx via P/Q- and L-type voltage-dependent calcium channels (VDCCs) while inhibiting N-type VDCCs.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Pharmacology

Background:

  • Peroxynitrite (OONO-) is a reactive nitrogen species implicated in neuronal damage.
  • Voltage-dependent calcium channels (VDCCs) play crucial roles in neuronal function and excitability.

Purpose of the Study:

  • To investigate the specific effects of peroxynitrite (OONO-) on different types of voltage-dependent calcium channels (VDCCs) in mouse cerebral cortical neurons.
  • To elucidate the mechanisms by which OONO- modulates calcium (Ca2+) influx.

Main Methods:

  • Measurement of 45Ca2+ influx into mouse cerebral cortical neurons.
  • Utilized specific blockers for different VDCC subtypes (nifedipine, omega-agatoxin VIA, omega-conotoxin GVIA).
  • Employed a peroxynitrite scavenger (manganese (III) tetrakis (4-benzoic acid) porphyrin) and depolarization stimulus (KCl).

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Main Results:

  • OONO- time- and dose-dependently increased Ca2+ influx, an effect blocked by the OONO- scavenger.
  • OONO- increased neuronal depolarization, indicated by bis-oxonol fluorescence.
  • Nifedipine and omega-agatoxin VIA inhibited OONO--induced Ca2+ influx, suggesting involvement of L-type and P/Q-type VDCCs, respectively.
  • OONO- inhibited KCl-induced Ca2+ influx, an effect similar to that of omega-conotoxin GVIA, indicating inhibition of N-type VDCCs.

Conclusions:

  • OONO- opens P/Q- and L-type VDCCs, leading to increased Ca2+ influx in neurons.
  • OONO- inhibits N-type VDCCs, reducing Ca2+ influx under depolarizing conditions.
  • These findings highlight the complex role of OONO- in regulating neuronal excitability through differential modulation of VDCCs.