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)
Kennedy
C
C
Department of Pharmacology, University of Cambridge, U.K.
Henderson
G
G
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008811:Mice, Inbred DBA; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017480:Receptors, sigma; D013469:Sulpiride / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D002227:Carbazoles; D015259:Dopamine Agents; D010880:Piperidines; D015221:Potassium Channels; D011957:Receptors, Opioid; D017480:Receptors, sigma; D013757:Tetraethylammonium Compounds; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D001285:Atropine; D013469:Sulpiride; C026539:preclamol; C034931:rimcazole