Voltage‐dependence of the human dopamine D₂ receptor

Abstract

The dopamine D2 receptor plays a critical role in activity-dependent synaptic plasticity in the striatum, and regulates the transitions between different states of electrical activity. The D2 receptor is the main target for antipsychotics, and its affinity towards dopamine has been shown to be increased in psychotic patients. Recently, voltage-sensitivity has been reported for the ligand binding and G protein-coupling properties of some neurotransmitter receptors, raising the question whether the D2 receptor is also regulated by voltage. Our present electrophysiology data from Xenopus oocytes indicate that the D2 receptor is indeed voltage-sensitive. Comparing concentration-response relationships for the activation of G protein-coupled inward rectifier potassium (GIRK) channels via D2 receptor stimulation by quinpirole or dopamine at -80 and at +40 mV revealed rightward shifts upon depolarisation of nearly tenfold, for both agonists. Our results are likely to bear relevance to the function of the D2 receptor in gating synaptic input and in regulating plasticity.