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 ace tylcholine receptor (nAChR)-mediated enhancement of spontaneous GABAergic i nhibitory postsynaptic currents (IPSCs) was investigated in chick brain sli ces. Whole cell recordings of neurons in the lateral spiriform (SpL) and ve ntral lateral geniculate (LGNv) nuclei showed that cadmium chloride (CdCl2) blocked the carbachol-induced increase of spontaneous GABAergic IPSCs, ind icating 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 GVI A, a selective antagonist of N-type channels, significantly reduced the nAC hR-mediated enhancement of gamma-aminobutyric acid (GABA) release in the Sp L by 78% compared with control responses. Nifedipine, an L-type channel blo cker, and omega-Agatoxin-TK, a P/Q-type channel blocker, did not inhibit th e enhancement of GABAergic IPSCs. In the LGNv, omega-Conotoxin GVIA also si gnificantly reduced the nAChR-mediated enhancement of GABA release by 71% f rom control values. Although omega-Agatoxin-TK did not block the nicotinic enhancement, L-type channel blockers showed complex effects on the nAChR-me diated enhancement. These results indicate that the nAChR-mediated enhancem ent of spontaneous GABAergic IPSCs requires activation of N-type channels i n both the SpL and LGNv.