CHARACTERIZATION OF THE CURRENTS INDUCED BY SIGMA-LIGANDS IN NCB20 NEUROBLASTOMA-CELLS

Electrical and pharmacological properties of currents induced by compo unds having affinities for putative sigma receptors were investigated with NCB20 cells by use of the whole-cell patch-clamp technique. Antip sychotics and naloxone induced inward currents with a decrease in memb rane conductance at a holding potential of -60 mV. The rank order of p otency for compounds inducing these currents was bromperidol > haloper idol > mosapramine - clocapramine, carpipramine > chlorpromazine > rem oxipride > naloxone. Sulpiride, which does not have affinity for sigma receptors, induced inward currents only slightly. Haloperidol-induced currents were not affected by the pretreatments with 10 mu M of sulpi ride, dopamine, atropine, N-methyl-D-aspartate, 2-amino-7-phosphonohep tanoic acid, morphine or A23187, 100 nM of ICS 205-930, 100 mu M of fo rskolin, 1 mu M of phorbol-12,13-dibutyrate, or 100 ng/ml of cholera o r pertussis toxins. The reversal potential of the currents induced by haloperidol, naloxone or remoxipride was dependent on the concentratio n of external or internal potassium. These results indicate that the c urrents induced by the tested compounds are due to blockade of tonic, outward potassium currents and suggest that these agents act on putati ve sigma receptors and that the second messenger systems within the ce ll are not essential for the coupling between the receptors and the ch annels.