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.
Sahlholm
Kristoffer
K
Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. kristoffer.sahlholm@ki.se
Marcellino
Daniel
D
Nilsson
Johanna
J
Fuxe
Kjell
K
Arhem
Peter
P
D000818:Animals; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D004594:Electrophysiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000819:agonists / Q000502:physiology; D006801:Humans; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D050638:Receptors, Dopamine D4 / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000819:agonists / Q000235:genetics / Q000502:physiology; D014981:Xenopus
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011993:Recombinant Fusion Proteins; C113776:dopamine D2L receptor; D050638:Receptors, Dopamine D4; D004298:Dopamine