title: D2 autoreceptors chronically enhance dopamine neuron pacemaker activity.
abstract: Activation of D2 autoreceptors on midbrain dopamine neurons has been shown previously to acutely open K+ channels to inhibit intrinsically generated pacemaker activity. Here we report that D2 autoreceptors act chronically to produce an opposite action: to increase the speed and regularity of repetitive action potential firing. Voltage-, current-, and dynamic-clamp experiments, using conventional whole-cell and perforated patch-clamp recording, with cultured rat midbrain dopamine neurons show that a change in the number of functional A-type K+ channels alters firing rate and susceptibility to irregularity produced by other channels. cAMP and protein kinase A mediate the long-term action of D2 receptors in a manner that counters the short-term effect of this signaling pathway on K+ channel gating. We conclude that D2 autoreceptors, in addition to mediating acute negative feedback, are responsible for long-term enhancement of the rate and fidelity of dopamine neuron pacemaker activity.
authors: Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors: Junghyun
authors: J
authors: Hahn
authors: Paul H M
authors: PH
authors: Kullmann
authors: John P
authors: JP
authors: Horn
authors: Edwin S
authors: ES
authors: Levitan