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 A2a 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 A2a adenosine receptors continued to open K(ATP) channels in ischemic pericytes. These results suggest that the regulation of K(ATP) channels via A1 and A2a receptors allows adenosine to serve over a broad range of metabolic conditions as a vasoactive signal in the retinal microvasculature.
Li
Q
Q
Department of Ophthalmology and Visual Sciences, The University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105, USA.
Puro
D G
DG
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D000968:Antimycin A / Q000494:pharmacology; D005136:Eye Proteins / Q000187:drug effects* / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D007461:Iodoacetates / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism; D020110:Pinacidil / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000502:physiology; D012171:Retinal Vessels / Q000187:drug effects* / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D000963:Antimetabolites; D005136:Eye Proteins; D007461:Iodoacetates; D015221:Potassium Channels; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D000968:Antimycin A; D020110:Pinacidil; D000255:Adenosine Triphosphate; D000241:Adenosine; D011188:Potassium; D005905:Glyburide