Work

Adenosine signaling activates ATP-sensitive K + channels in endothelial cells and pericytes in CNS capillaries

Year: 2022

Type: article

Abstract: SUMMARY The dense network of capillaries composed of capillary endothelial cells (cECs) and pericytes lies in close proximity to all neurons, ideally positioning it to sense neuro/glial-derived compounds that regulate regional and global cerebral perfusion. The membrane potential (V M ) of vascular cells serves as the essential output in this scenario, linking brain activity to vascular function. The ATP-sensitive K + channel (K ATP ) is a key regulator of vascular V M in other beds, but whether brain capillaries possess functional K ATP channels remains unknown. Here, we demonstrate that brain capillary ECs and pericytes express K ATP channels that robustly control V M . We further show that the endogenous mediator adenosine acts through A 2A receptors and the G s /cAMP/PKA pathway to activate capillary K ATP channels. Moreover, K ATP channel stimulation in vivo causes vasodilation and increases cerebral blood flow (CBF). These findings establish the presence of K ATP channels in cECs and pericytes and suggest their significant influence on CBF. HIGHLIGHTS Capillary network cellular components—endothelial cells and pericytes—possess functional K ATP channels. Activation of K ATP channels causes profound hyperpolarization of capillary cell membranes. Capillary K ATP channels are activated by exogenous adenosine via A 2A receptors and cAMP-dependent protein kinase. K ATP channel activation by adenosine or synthetic openers increases cerebral blood flow.

Source: Science Signaling

DOI: 10.1126/scisignal.abl5405