Adenosine activates ATP-sensitive K currents in pericytes of rat retinal microvessels: role of A1 and A2a receptors

In the CNS, contractile pericytes are positioned on the endothelial walls of microvessels where they are thought to play a role in adjusting blood flow to meet local metabolic needs. This function may be particularly important in the retina where pericytes are more numerous than at any other site. Despite the putative importance of pericytes, knowledge of the mechanisms by which vasoactive molecules, such as adenosine, regulate their function is limited. Using the perforated-patch configuration of the patch-clamp technique to monitor the whole-cell currents of pericytes located on microvessels freshly isolated from the adult rat retina, we found that adenosine reversibly activated a hyperpolarizing current in 98% of the sampled pericytes. This adenosine-induced current is likely to be due to the opening of ATP-sensitive potassium (K_ATP) channels since it had a reversal potential near the equilibrium potential for K⁺, was inhibited by the K_ATP channel blocker, glibenclamide, and was mimicked by pinacidil, which is a K_ATP channel opener. Experiments with specific agonists and antagonists indicated that both the high affinity A₁ and the lower affinity A_2a adenosine receptors provided effective pathways for activating K_ATP currents in pericytes recorded under normal metabolic conditions. However, during chemical ischemia, the A₁ receptor pathway rapidly became ineffective. In contrast, activation of A_2a adenosine receptors continued to open K_ATP channels in ischemic pericytes. These results suggest that the regulation of K_ATP channels via A₁ and A_2a receptors allows adenosine to serve over a broad range of metabolic conditions as a vasoactive signal in the retinal microvasculature.