High-affinity inhibition of glutamate release from corticostriatal synapses by omega-agatoxin TK

Eur J Pharmacol. 2001 Nov 2;430(2-3):167-73. doi: 10.1016/s0014-2999(01)01388-7.

Abstract

To know which Ca(2+) channel type is the most important for neurotransmitter release at corticostriatal synapses of the rat, we tested Ca(2+) channel antagonists on the paired pulse ratio. omega-Agatoxin TK was the most effective Ca(2+) channel antagonist (IC(50)=127 nM; maximal effect=211% (with >1 microM) and Hill coefficient=1.2), suggesting a single site of action and a Q-type channel profile. Corresponding parameters for Cd(2+) were 13 microM, 178% and 1.2. The block of L-type Ca(2+) channels had little impact on transmission, but we also tested facilitation of L-type Ca(2+) channels. The L-type Ca(2+) channel agonist, s-(-)-1,4 dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-3-pyridine carboxylic acid methyl ester (Bay K 8644 (5 microM)), produced a 45% reduction of the paired pulse ratio, suggesting that even if L-type channels do not participate in the release process, they may participate in its modulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Agatoxins
  • Animals
  • Cadmium / pharmacology
  • Calcium / pharmacology
  • Calcium Channel Blockers / pharmacology*
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / physiology
  • Corpus Striatum / drug effects*
  • Corpus Striatum / physiology
  • Dose-Response Relationship, Drug
  • Glutamic Acid / metabolism*
  • In Vitro Techniques
  • Male
  • Rats
  • Rats, Wistar
  • Spider Venoms / pharmacology*
  • Synapses / drug effects*
  • Synapses / metabolism
  • omega-Conotoxin GVIA / pharmacology

Substances

  • Agatoxins
  • Calcium Channel Blockers
  • Spider Venoms
  • omega-agatoxin-Aa4b
  • Cadmium
  • Glutamic Acid
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • omega-Conotoxin GVIA
  • Calcium