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.