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 D(2L) receptor and we now extend our studies to include the other members of the D(2)-like receptor subfamily; the D(2S), D(3), and D(4) dopamine receptors. Electrophysiological recordings were performed on Xenopus oocytes coexpressing human dopamine D(2S), D(3), or D(4) 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 D(2S) and D(4) upon depolarization. In contrast, the concentration-response relationships for D(3)-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.