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

Cholinergic presynaptic inhibition was investigated on neostriatal glutamat ergic transmission, Paired pulse facilitation (PPF) of orthodromic populati on spikes (PS) were used to construct a concentration-response relationship for muscarine on presynaptic inhibition, Muscarine had an effect proportio nal to its extracellular concentration with an EC50 (mean a standard estima tion error) of: 2.5 +/- 1.5 nM, and a maximal effect (saturation) of 245 +/ - 16%, Several peptidic toxins against some voltage-gated Ca2+-channels inc reased PPF indicating that the Ca2+-channels they block participate in tran smitter release. However, neither 1 mu M omega-conotoxin GVIA, a specific b locker 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 co nsistent with Q-type Ca2+-channels mediating muscarinic presynaptic inhibit ion of neostriatal afferents, (C) 1999 Elsevier Science Inc.