Inhibition of potassium currents by the sigma receptor ligand (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine in sympathetic neurons of the mouse isolated hypogastric ganglion.

The actions of (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)3-PPP] on sympathetic neurons of the mouse isolated hypogastric ganglion were studied using the current clamp and single electrode voltage clamp techniques. In neurons studied under current clamp (+)3-PPP (10(-5) to 3 x 10(-4) M) evoked a concentration-dependent depolarization, which was fully reversible on washout of the drug. The depolarization was associated with an increase in membrane input resistance. At membrane potentials between -43 and -65 mV the amplitude of the depolarization was inversely related to the membrane potential. (+)3-PPP had no effect on membrane potential at potentials negative to -65 mV. The effect of (+)3-PPP on the M-current was studied in cells voltage clamped at -40 mV and stepped to -60 mV for 300-500 ms. The slow current relaxations seen during and after the voltage step are largely due to the M-current. (+)3-PPP (3 x 10(-5) to 3 x 10(-4) M) inhibited the M-current and produced an inward current in a concentration-dependent manner. (-)3-PPP (3 x 10(-5) M) had similar effects, but was less potent than (+)3-PPP. (+)3-PPP (3 x 10(-5) M) also inhibited the A-current and a calcium-dependent potassium current, but to a lesser degree than the M-current.(ABSTRACT TRUNCATED AT 250 WORDS)