Muscarinic presynaptic inhibition of neostriatal glutamatergic afferents is mediated by Q-type Ca2+ channels.

Cholinergic presynaptic inhibition was investigated on neostriatal glutamatergic transmission. Paired pulse facilitation (PPF) of orthodromic population spikes (PS) were used to construct a concentration-response relationship for muscarine on presynaptic inhibition. Muscarine had an effect proportional to its extracellular concentration with an EC50 (mean +/- standard estimation error) of: 2.5 +/- 1.5 nM, and a maximal effect (saturation) of 245 +/- 16%. Several peptidic toxins against some voltage-gated Ca2+-channels increased PPF indicating that the Ca2+-channels they block participate in transmitter release. However, neither 1 microM omega-conotoxin GVIA, a specific blocker of N-type Ca2+-channels, nor 10-30 nM omega-agatoxinTK, a selective blocker of P-type Ca2+-channels, were able to occlude muscarine's effect on presynaptic inhibition. Nevertheless, 100-400 nM omega-agatoxinTK occluded muscarine's action on PPF in a dose-dependent manner. These results are consistent with Q-type Ca2+-channels mediating muscarinic presynaptic inhibition of neostriatal afferents.