Abstract
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, Ca2+-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 Ca2+-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 Ca2+-channels of SPNs as final effectors. Our hypotheses are that modulation of Ca2+-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 Ca2+-currents in all SPNs tested. However, A2A-type receptors enhanced Ca2+-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 Ca2+-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.
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Acknowledgments
We thank Antonio Laville, Gabriela X. Ayala, Adriana Hernandez, Mariana Duhne, Ernesto A. Rendon, and Dagoberto Tapia for technical support and advice and to Dr. Claudia Rivera for animal care.
Financial disclosure related to research covered in this article
This work was supported by the Consejo Nacional de Ciencia y Tecnología [CONACyT-México] grants 154131 and 98004 to JB and EG, respectively, by grants from Dirección General de Asuntos del Personal Académico. Universidad Nacional Autónoma de México (DGAPA-UNAM) to JB and EG, respectively, and by the Mexico-Germany Agreement Consejo Nacional de Ciencia y Tecnología-Deutsche Forschungsgemeinschaft (CONACyT-DFG) Grant I0110/193/10 FON.INST.-29-10 to JB. Hernandez-Gonzalez O, Hernandez-Flores T and Arias-Garcia M have CONACyT doctoral fellowships. Data in this work are part of O H-G doctoral dissertation in the Posgrado en Ciencias Biomédicas de la Universidad Nacional Autónoma de México. Prieto GA and Perez-Burgos A were graduate students in the same institution and had CONACyT doctoral fellowships. No conflicts of interest are declared.
Financial disclosures of all authors [for the preceding 12 months]
Hernandez-Gonzalez O: Graduate student with a CONACyT scholarship.
Hernandez-Flores T: Graduate student with a CONACyT scholarship.
Prieto GA: On postdoctoral residence.
Perez-Burgos A: On postdoctoral residence.
Arias-García M: Graduate student with a CONACyT scholarship
Bargas J: Universidad Nacional Autónoma de México, Professor.
Galarraga E: Universidad Nacional Autónoma de México, Professor.
Documentation of author roles
Hernandez-Gonzalez O: Design, execution of experiments, statistical analysis, and writing of the first draft of the manuscript. Hernandez-Flores T: execution of experiments. Arias-García M: execution of experiments. Prieto GA, Perez-Burgos A: execution of first experiments and assessment of viability. Bargas J: Conception, design, and organization of the research project. Galarraga E: Review, critique, and final organization of the manuscript.
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Hernández-González, O., Hernández-Flores, T., Prieto, G.A. et al. Modulation of Ca2+-currents by sequential and simultaneous activation of adenosine A1 and A2A receptors in striatal projection neurons. Purinergic Signalling 10, 269–281 (2014). https://doi.org/10.1007/s11302-013-9386-z
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DOI: https://doi.org/10.1007/s11302-013-9386-z