PT  - JOURNAL ARTICLE
AU  - Junghyun Hahn
AU  - Paul H. M. Kullmann
AU  - John P. Horn
AU  - Edwin S. Levitan
TI  - D<sub>2</sub> Autoreceptors Chronically Enhance Dopamine Neuron Pacemaker Activity
AID  - 10.1523/JNEUROSCI.4976-05.2006
DP  - 2006 May 10
TA  - The Journal of Neuroscience
PG  - 5240--5247
VI  - 26
IP  - 19
4099  - http://www.jneurosci.org/content/26/19/5240.short
4100  - http://www.jneurosci.org/content/26/19/5240.full
SO  - J. Neurosci.2006 May 10; 26
AB  - 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.