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 A2A receptors are Gs-coupled P1 purinergic receptors which are widely distributed throughout the CNS. It has been demonstrated that OPCs express A2A 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 A2A receptors on membrane currents and differentiation of purified primary OPCs isolated from the rat cortex. We found that the selective A2A agonist, CGS21680, inhibits sustained, delayed rectifier, K+ currents (IK) without modifying transient (IA) conductances. The effect was observed in all cells tested, independently from time in culture. CGS21680 inhibition of IK current was concentration-dependent (10–200 nM) and blocked in the presence of the selective A2A antagonist SCH58261 (100 nM).It is known that IK 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 A2A 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 A2A receptors whose activation negatively modulate IK currents. We propose that, by this mechanism, A2A adenosine receptors inhibit OPC differentiation.