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

To know which Ca2+ channel type is the most important for neurotransmitter release at corticostriatal synapses of the rat, we tested Ca2+ channel antagonists on the paired pulse ratio. omega -Agatoxin TK was the most effective Ca2+ channel antagonist (IC50 = 127 nM; maximal effect = 211% (with > 1 muM) and Hill coefficient = 1.2), suggesting a single site of action and a Q-type channel profile. Corresponding parameters for Cd2+ were 13 muM, 178% and 1.2. The block of L-type Ca2+ channels had little impact on transmission, but we also tested facilitation of L-type Ca2+ channels. The L-type Ca2+ 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 muM)), 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. (C) 2001 Elsevier Science B.V. All rights reserved.