Opioid receptor independent inhibition of Ca2+ and K+ currents in NG108-15 cells by the kappa opioid receptor agonist U50488H

THE whole-cell patch clamp technique was used to investigate the actions of the opioid agonist U50488H on Ca2+ and K+ currents in differentiated NG108-15 cells. U50488H (5-50 mu M) caused a concentration-dependent, reversible inhibition of high voltage-activated Ca2+ currents which persisted in the presence of nifedipine (2 mu M), indicating a blockade of N-type Ca2+ channels. The actions of U50488H were also observed in the presence of 30 mu M naloxone, which fully abolished current inhibition caused by a selective delta opioid receptor agonist. U50488H also inhibited Ca2+-insensitive, voltage-gated K+ currents in NG108-15 cells in the presence of naloxone. Our results indicate that U50488H can inhibit neuronal ionic channels via a mechanism which does not involve activation of kappa opioid receptors.