N-type voltage-dependent calcium channels mediate the nicotinic enhancement of GABA release in chick brain.
The role of voltage-dependent calcium channels (VDCCs) in the nicotinic acetylcholine receptor (nAChR)-mediated enhancement of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) was investigated in chick brain slices. Whole cell recordings of neurons in the lateral spiriform (SpL) and ventral lateral geniculate (LGNv) nuclei showed that cadmium chloride (CdCl2) blocked the carbachol-induced increase of spontaneous GABAergic IPSCs, indicating that VDCCs might be involved. To conclusively show a role for VDCCs, the presynaptic effect of carbachol on SpL and LGNv neurons was examined in the presence of selective blockers of VDCC subtypes. omega-Conotoxin GVIA, a selective antagonist of N-type channels, significantly reduced the nAChR-mediated enhancement of gamma-aminobutyric acid (GABA) release in the SpL by 78% compared with control responses. Nifedipine, an L-type channel blocker, and omega-Agatoxin-TK, a P/Q-type channel blocker, did not inhibit the enhancement of GABAergic IPSCs. In the LGNv, omega-Conotoxin GVIA also significantly reduced the nAChR-mediated enhancement of GABA release by 71% from control values. Although omega-Agatoxin-TK did not block the nicotinic enhancement, L-type channel blockers showed complex effects on the nAChR-mediated enhancement. These results indicate that the nAChR-mediated enhancement of spontaneous GABAergic IPSCs requires activation of N-type channels in both the SpL and LGNv.
Department of Pharmacology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
T L
TL
Tredway
J Z
JZ
Guo
V A
VA
Chiappinelli
D060848:Agatoxins; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D019256:Cadmium Chloride / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002642:Chick Embryo; D005071:Evoked Potentials / Q000187:drug effects; D005829:Geniculate Bodies / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D018722:Nicotinic Agonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D060848:Agatoxins; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D013111:Spider Venoms; C083855:omega-agatoxin-Aa4b; D005680:gamma-Aminobutyric Acid; D002217:Carbachol; D019256:Cadmium Chloride