Ž . European Journal of Pharmacology 430 2001 167–173 www.elsevier.comrlocaterejphar High-affinity inhibition of glutamate release from corticostriatal synapses by v-agatoxin TK Jaime Barral a , Francisco Poblette a , Ernesto Mendoza a , Juan C. Pineda b , Elvira Galarraga c , Jose Bargas c, ) ´ a Neurociencias, FES Iztacala, UNAM, Estado de Mexico, Mexico b Centro de InÕestigaciones Regionales, UADY, Merida, Yucatan, Mexico ´ ´ c Instituto de Fisiologıa Celular, P.O. Box 70-253, UNAM, Mexico City DF 04510, Mexico ´ Received 15 February 2001; received in revised form 6 September 2001; accepted 7 September 2001 Abstract To know which Ca 2q channel type is the most important for neurotransmitter release at corticostriatal synapses of the rat, we tested 2q 2q Ž Ca channel antagonists on the paired pulse ratio. v-Agatoxin TK was the most effective Ca channel antagonist IC s127 nM; 50 Ž . . maximal effect s211% with )1 mM and Hill coefficient s1.2 , suggesting a single site of action and a Q-type channel profile. Corresponding parameters for Cd 2q were 13 mM, 178% and 1.2. The block of L-type Ca 2q channels had little impact on transmission, 2q 2q Ž . w but we also tested facilitation of L-type Ca channels. The L-type Ca channel agonist, s- y -1,4 dihydro-2,6-dimethyl-5-nitro-4- 2- Ž . x Ž Ž .. trifluoromethyl phenyl -3-pyridine carboxylic acid methyl ester Bay K 8644 5 mM , 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. q 2001 Elsevier Science B.V. All rights reserved. Keywords: v-Agatoxin TK; v-Conotoxin GVIA; Synaptic transmission; Neostriatum; Ca 2q channel 1. Introduction Changes in the paired pulse ratio obtained from a pair of orthodromic responses mainly reflect the non-linearity Ž of the presynaptic processes of transmission Zucker, 1989, . 1999 . Postsynaptic processes do not change the paired pulse ratio under most circumstances but change both Ž orthodromic responses in the same proportion Dunwiddie . and Hass, 1985 . A postsynaptic process also changes the antidromic response. Consequently, the paired pulse ratio associated with field population spike recordings is a reliable protocol that can be used to pharmacologically screen receptors located at presynaptic nerve terminals Ž e.g., Creager et al., 1980; Dunwiddie and Hass, 1985; Malenka and Kocsis, 1988; Kahle and Cotman, 1993; Lovinger et al., 1993; Wheeler et al., 1994; Ameri et al., . 1999; Barral et al., 1999, 2000 . The results obtained with this protocol have been corroborated with other techniques Ž such as intracellular- and whole-cell recordings Nisen- ) Corresponding author. Tel.: q 52-5-622-5670; fax: q 52-5-622-5607. Ž . E-mail address: jbargas@ifisiol.unam.mx J. Bargas . baum et al., 1992; Lovinger et al., 1993; Brundege and Dunwiddie, 1996; Hernandez-Echeagaray et al., 1998; Sul- ´ . livan, 1999; Gerdeman and Lovinger, 2001 . In this work, the paired pulse ratio was used to test Ca 2q channel-targeting ligands whose actions are known Ž to be located at corticostriatal terminals Turner et al., 1993; Lovinger et al., 1994; Bargas et al., 1998; Hill and . Brotchie, 1999 . A main goal was to perform a concentra- tion–response analysis for v-agatoxin TK in corticostriatal terminals. Pharmacological analyses of Ca 2q channel an- tagonists based on the paired pulse ratio coincided with previous results obtained with different techniques and Ž other central neurons Takahashi and Momiyama, 1993; Wheeler et al., 1994; Teramoto et al., 1995, 1997; Reid et al., 1998; Iwasaki et al., 2000; Turner et al., 1993; Luebke . et al., 1993; Dooley et al., 2000 . There is consensus about the importance of PrQ-type 2q Ž . Ca channels a in the release process. We performed 1A a concentration–response analysis of v-agatoxin TK to ascertain whether the profile obtained is more similar to the P-type or the Q-type channel-blocking profile. Recent evidence has suggested a strong convergence of presynap- 2q Ž tic modulators at Q-type Ca channels Wheeler et al., 0014-2999r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. Ž . PII: S0014-2999 01 01388-7