μ Opioid Receptors Modulate Action Potential Kinetics and Firing Frequency in Neocortical Interneurons

Abstract

The endogenous opioid system of the cerebral cortex is an important feature of antinociception and reward valuation through its modulation of inhibitory neocortical interneurons. Dysregulation of this system, through disease or drugs, disrupts the reward system and contributes to eating and mood disorders, impulsive actions, and addiction. Impulsive behaviors can be induced experimentally through infusion of the opioid receptor specific agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin (DAMGO) into the frontal cortex in animal models. The mechanism involves increased potassium channel function, which suppresses neocortical interneuron activity. However, much of the data on the effect of this receptor on ion channels have been derived from noncortical ORs, and the identity and effects of the ion channels that the OR targets in neocortical neurons have not been thoroughly investigated. Based on previous experiments by other labs, we hypothesized that the OR could activate -dendrotoxin (DTX) sensitive channels (Kv1.1, Kv1.2, and Kv1.6 subunits) to exert its inhibitory effects in cortical interneurons. This, in turn, is expected to confer a variety of effects on passive and active electrical properties of the cell. We performed patch-clamp electrophysiology to examine the electrophysiological effects of ORs in cultured neocortical interneurons. We found that a range of features among the 54 membrane and action potential properties we analyzed were modulated by ORs, including action potential kinetics and frequency. The Kv1.1, Kv1.2, and Kv1.6 inhibitor DTX reversed some effects on action potential frequency, but not effects on their kinetics. Therefore, ORs in neocortical interneurons influence DTX-sensitive channels, as well as other channels, to modulate action potential kinetics and firing properties.