Inhibitory effects of psychotomimetic σ ligands on nicotine-induced K + flux from differentiated PC12 cells

In NGF-treated PC12 cells, nicotine-induced K + release was measured with a K +-sensitive microelectrode. The K + outflow via nicotinic ACh receptor cation channels was inhibited by various psychotomimetic σ ligands in the sequence of PCP, dextromethorphan >> DTG, MK 801, (+)SKF10047 >> (+)3-PPP. The K + release was not affected by the neuroleptic sigma ligand haloperidol nor by the calcium antagonist nifedipine. The results suggest that psychotomimetic sigma ligands inhibit nicotine-stimulated K + flux by interacting with nicotinic, rather than via σ 2 receptors.