Suppression of Ca2+ influx through L-type voltage-dependent calcium channels by hydroxyl radical in mouse cerebral cortical neurons

Brain Res Mol Brain Res. 2001 Aug 15;92(1-2):12-8. doi: 10.1016/s0169-328x(01)00128-0.

Abstract

In the present study, we investigated the effect of hydroxyl radical (.OH) produced by the Fenton reaction with FeSO(4) to H(2)O(2) on Ca2+ influx by measuring [(45)Ca2+] influx into mouse cerebral cortical neurons in primary culture.OH formed from 3 microM FeSO(4) and 0.01 microM H(2)O(2) significantly reduced 30 mM KCl-induced [(45)Ca2+] influx and this reduction was abolished by .OH scavengers such as N,N'-dimethylthiourea and mannitol. Nifedipine (1 microM), an inhibitor for L-type voltage-dependent Ca2+ channels (VDCCs) showed no additive effect on the reduction of the 30 mM KCl-induced [(45)Ca2+] influx, while the inhibitors for P/Q- and N-type VDCCs showed further suppression of the KCl-induced [(45)Ca2+] influx even in the presence of .OH. Bay k 8644, an activator of L-type VDCCs, dose-dependently stimulated [(45)Ca2+] influx, and this stimulation disappeared in the presence of nifedipine. Similarly, .OH also suppressed significantly [(45)Ca2+] influx induced by Bay k 8644. These inhibitory actions of .OH on the KCl- and Bay k 8644-induced [(45)Ca2+] influx were completely abolished by .OH scavengers. These results indicate that .OH has the activity to suppress Ca2+ influx through L-type VDCCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Animals
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / classification
  • Calcium Channels / drug effects
  • Calcium Channels, L-Type / drug effects*
  • Calcium Channels, L-Type / metabolism
  • Calcium Signaling / drug effects*
  • Cells, Cultured / drug effects
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / metabolism
  • Deferoxamine / pharmacology
  • Ferrous Compounds / pharmacology
  • Free Radical Scavengers / pharmacology
  • Hydrogen Peroxide / pharmacology
  • Hydroxyl Radical / pharmacology*
  • Ion Channel Gating
  • Ion Transport / drug effects
  • Iron Chelating Agents / pharmacology
  • Mannitol / pharmacology
  • Mice
  • Nerve Tissue Proteins / drug effects*
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects*
  • Neurons / metabolism
  • Nifedipine / pharmacology
  • Potassium Chloride / pharmacology
  • Thiourea / analogs & derivatives*
  • Thiourea / pharmacology
  • omega-Agatoxin IVA / pharmacology
  • omega-Conotoxin GVIA / pharmacology

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Channels, L-Type
  • Ferrous Compounds
  • Free Radical Scavengers
  • Iron Chelating Agents
  • Nerve Tissue Proteins
  • omega-Agatoxin IVA
  • Hydroxyl Radical
  • ferrous sulfate
  • Mannitol
  • Potassium Chloride
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • 1,3-dimethylthiourea
  • omega-Conotoxin GVIA
  • Hydrogen Peroxide
  • Thiourea
  • Nifedipine
  • Deferoxamine
  • Calcium