Differential voltage-sensitivity of D2-like dopamine receptors

Agonist potency at some neurotransmitter receptors has been shown to be regulated by transmembrane voltage, a mechanism which has been suggested to play a crucial role in the regulation of neurotransmitter release by autoreceptors and in synaptic plasticity. We have recently described the voltage-sensitivity of the dopamine D2L receptor and we now extend our studies to include the other members of the D2-like receptor subfamily; the D2S, D3, and D4 dopamine receptors. Electrophysiological recordings were performed on Xenopus oocytes coexpressing human dopamine D2S, D3, or D4 receptors with G protein-coupled potassium (GIRK) channels. Comparison of concentration–response relationships at −80 mV and at 0 mV for dopamine-mediated GIRK activation revealed significant rightward shifts for both D2S and D4 upon depolarization. In contrast, the concentration–response relationships for D3-mediated GIRK activation were not appreciably different at the two voltages. Our findings provide new insight into the functional differences of these closely related receptors.