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.
Barral
J
J
Neurociencias, ENEP Iztacala, UNAM, México City, México.
Galarraga
E
E
Bargas
J
J
D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D009116:Muscarine / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects*; D009433:Neural Inhibition; D010455:Peptides / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000037:antagonists & inhibitors; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018721:Muscarinic Agonists; D010455:Peptides; D017661:Receptors, Presynaptic; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D018698:Glutamic Acid; D009116:Muscarine; D020866:omega-Conotoxin GVIA