Abstract
The actions of the opioid agonist U50488H on I A and I K 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 I A and I K. The inhibitory actions were still observed in the presence of 30 μM naloxone or 5 μM nor-binaltorphimine dihydrochloride. The IC 50 values for the blockade of I A and I K were calculated as 20.1.9 and 3.7 μM, respectively. In the presence of 3.3 μM U50488H, repetitive stimulation induced use-dependent inhibition of I A and I K. A 10 μM concentration of U50488H positively shifted the half-activation membrane potential of I A by +11 mV, but negatively shifted I K by −14 mV. These results demonstrate that U50488H can directly inhibit neuronal I A and I K without involvement of the activation of κ-opioid receptors.
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