Blockade of U50488H on potassium currents of acutely isolated mouse hippocampal CA3 pyramidal neurons.

The actions of the opioid agonist U50488H on IA and IK were examined in acutely isolated mouse hippocampal CA3 pyramidal neurons using the whole-cell patch clamp technique. U50488H caused a concentration dependent, rapidly developing and reversible inhibition of voltage-activated IA and IK. The inhibitory actions were still observed in the presence of 30 microM naloxone or 5 microM nor-binaltorphimine dihydrochloride. The IC50 values for the blockade of IA and IK were calculated as 20.1.9 and 3.7 microM, respectively. In the presence of 3.3 microM U50488H, repetitive stimulation induced use-dependent inhibition of IA and IK. A 10 microM concentration of U50488H positively shifted the half-activation membrane potential of IA by +11 mV, but negatively shifted IK by -14 mV. These results demonstrate that U50488H can directly inhibit neuronal IA and IK without involvement of the activation of kappa-opioid receptors.