title: Adenosine A₂A receptors inhibit delayed rectifier potassium currents and cell differentiation in primary purified oligodendrocyte cultures.
abstract: Oligodendrocyte progenitor cells (OPCs) are a population of cycling cells which persist in the adult central nervous system (CNS) where, under opportune stimuli, they differentiate into mature myelinating oligodendrocytes. Adenosine A(2A) receptors are Gs-coupled P1 purinergic receptors which are widely distributed throughout the CNS. It has been demonstrated that OPCs express A(2A) receptors, but their functional role in these cells remains elusive. Oligodendrocytes express distinct voltage-gated ion channels depending on their maturation. Here, by electrophysiological recordings coupled with immunocytochemical labeling, we studied the effects of adenosine A(2A) receptors on membrane currents and differentiation of purified primary OPCs isolated from the rat cortex. We found that the selective A(2A) agonist, CGS21680, inhibits sustained, delayed rectifier, K(+) currents (I(K)) without modifying transient (I(A)) conductances. The effect was observed in all cells tested, independently from time in culture. CGS21680 inhibition of I(K) current was concentration-dependent (10-200 nM) and blocked in the presence of the selective A(2A) antagonist SCH58261 (100 nM). It is known that I(K) currents play an important role during OPC development since their block decreases cell proliferation and differentiation. In light of these data, our further aim was to investigate whether A(2A) receptors modulate these processes. CGS21680, applied at 100 nM in the culture medium of oligodendrocyte cultures, inhibits OPC differentiation (an effect prevented by SCH58261) without affecting cell proliferation. Data demonstrate that cultured OPCs express functional A(2A) receptors whose activation negatively modulate I(K) currents. We propose that, by this mechanism, A(2A) adenosine receptors inhibit OPC differentiation.
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Division of Pharmacology and Toxicology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Coppi
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Cellai
authors.forename: Giovanna
authors.initials: G
authors.lastname: Maraula
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Pugliese
authors.forename: Felicita
authors.initials: F
authors.lastname: Pedata
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D051668:Delayed Rectifier Potassium Channels / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology*; D010627:Phenethylamines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D061251:Primary Cell Culture; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D014230:Triazoles / Q000494:pharmacology
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D051668:Delayed Rectifier Potassium Channels; D010627:Phenethylamines; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D014230:Triazoles; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine; D011188:Potassium
keywords: 2-(2-Furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine; 4-[2-[[6-Amino-9-(N-ethyl-β-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzene propanoic acid; Adenosine A(2A) receptors; CGS21680; DMSO; I(A); I(K); K(+) currents; Myelination; OPC; Oligodendrocyte differentiation; SCH58261; TEA; TTX; delayed rectifier K(+) current; dimethyl sulphoxide; oligodendrocyte progenitor cell; tetraethylammonium; tetrodotoxin; transient K(+) current