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Hernández-González, O; Hernández-Flores, T; Prieto, GA; Pérez-Burgos, A; Arias-García, MA; Galarraga, E; Bargas, J (2014)

MODULATION OF CA2+-CURRENTS BY SEQUENTIAL AND SIMULTANEOUS ACTIVATION OF ADENOSINE A1 AND A2A RECEPTORS IN STRIATAL PROJECTION NEURONS

Purinergic Signalling 10():269-281
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D1- and D2-types of dopamine receptors are located separately in direct and indirect pathway striatal projection neurons (dSPNs and iSPNs). In comparison, adenosine A1-type receptors are located in both neuron classes, and adenosine A2A-type receptors show a preferential expression in iSPNs. Due to their importance for neuronal excitability, Ca(2+)-currents have been used as final effectors to see the function of signaling cascades associated with different G protein-coupled receptors. For example, among many other actions, D1-type receptors increase, while D2-type receptors decrease neuronal excitability by either enhancing or reducing, respectively, CaV1 Ca(2+)-currents. These actions occur separately in dSPNs and iSPNs. In the case of purinergic signaling, the actions of A1- and A2A-receptors have not been compared observing their actions on Ca(2+)-channels of SPNs as final effectors. Our hypotheses are that modulation of Ca(2+)-currents by A1-receptors occurs in both dSPNs and iSPNs. In contrast, iSPNs would exhibit modulation by both A1- and A2A-receptors. We demonstrate that A1-type receptors reduced Ca(2+)-currents in all SPNs tested. However, A2A-type receptors enhanced Ca(2+)-currents only in half tested neurons. Intriguingly, to observe the actions of A2A-type receptors, occupation of A1-type receptors had to occur first. However, A1-receptors decreased CaV2 Ca(2+)-currents, while A2A-type receptors enhanced current through CaV1 channels. Because these channels have opposing actions on cell discharge, these differences explain in part why iSPNs may be more excitable than dSPNs. It is demonstrated that intrinsic voltage-gated currents expressed in SPNs are effectors of purinergic signaling that therefore play a role in excitability.