KAPPA-OPIOID RECEPTORS ALSO INCREASE POTASSIUM CONDUCTANCE

Decrease of calcium conductance induced by opioid agonists has been reported by others for mu-, delta, and kappa-opioid receptors. On the other hand, only mu- and delta-opioid receptors have been reported to increase potassium conductance. Intracellular recordings were made from guinea pig substantia gelatinosa neurons in a brain slice. A subset of cells (29 of 83) were hyperpolarized by the kappa-opioid receptor agonist U69593 with an EC50 of 23 nM. The kappa-opioid receptor antagonist norbinaltorphimine (10 nM) blocked the hyperpolarization by U69593 but had no effect on the mu-opioid hyperpolarization present in these cells. Naloxone (300 nM) shifted the U69593 dose-response curve to the right, giving an estimated K(d) for naloxone of 7.5 and 8.1 nM measured in two cells. The hyperpolarization caused by U69593 was mediated by a potassium conductance as determined with voltage clamp experiments. This demonstrates, depending on the cell type, that all three major opioid receptors (mu, delta, and kappa) can increase potassium conductance as well as decrease calcium conductance.