D1 receptors physically interact with N-type calcium channels to regulate channel distribution and dendritic calcium entry.
Dopamine signaling through D1 receptors in the prefrontal cortex (PFC) plays a critical role in the maintenance of higher cognitive functions, such as working memory. At the cellular level, these functions are predicated to involve alterations in neuronal calcium levels. The dendrites of PFC neurons express D1 receptors and N-type calcium channels, yet little information exists regarding their coupling. Here, we show that D1 receptors potently inhibit N-type channels in dendrites of rat PFC neurons. Using coimmunoprecipitation, we demonstrate the existence of a D1 receptor-N-type channel signaling complex in this region, and we provide evidence for a direct receptor-channel interaction. Finally, we demonstrate the importance of this complex to receptor-channel colocalization in heterologous systems and in PFC neurons. Our data indicate that the N-type calcium channel is an important physiological target of D1 receptors and reveal a mechanism for D1 receptor-mediated regulation of cognitive function in the PFC.
Kisilevsky
Alexandra E
AE
Department of Physiology and Biophysics, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive Northwest, Calgary, Canada.
Mulligan
Sean J
SJ
Altier
Christophe
C
Iftinca
Mircea C
MC
Varela
Diego
D
Tai
Chao
C
Chen
Lina
L
Hameed
Shahid
S
Hamid
Jawed
J
Macvicar
Brian A
BA
Zamponi
Gerald W
GW
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000502:physiology*; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D017397:Prefrontal Cortex / Q000166:cytology; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D014162:Transfection / Q000379:methods
C503279:Cacna1b protein, rat; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D015259:Dopamine Agents; D017447:Receptors, Dopamine D1; D002118:Calcium; D004298:Dopamine