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Adenosine signaling activates ATP-sensitive K channels in endothelial cells and pericytes in CNS capillaries. | LitMetric

AI Article Synopsis

  • Capillary endothelial cells (cECs) and pericytes form a dense network of capillaries that closely interact with neurons, playing a key role in sensing compounds that regulate blood flow in the brain.
  • A dominant-negative mutant of the K channel subunit was created in transgenic mice, revealing that K channels in both cECs and pericytes significantly influence brain vascular function.
  • Activation of capillary K channels by adenosine through specific signaling pathways enhances cerebral blood flow, indicating their critical role in cerebral perfusion regulation.

Article Abstract

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 neuron- and glial-derived compounds that enhance regional and global cerebral perfusion. The membrane potential () of vascular cells serves as the physiological bridge that translates brain activity into vascular function. In other beds, the ATP-sensitive K (K) channel regulates in vascular smooth muscle, which is absent in the capillary network. Here, with transgenic mice that expressed a dominant-negative mutant of the pore-forming Kir6.1 subunit specifically in brain cECs or pericytes, we demonstrated that K channels were present in both cell types and robustly controlled . We further showed that the signaling nucleotide adenosine acted through A receptors and the Gα/cAMP/PKA pathway to activate capillary K channels. Moreover, K channel stimulation in vivo increased cerebral blood flow (CBF), an effect that was blunted by expression of the dominant-negative Kir6.1 mutant in either capillary cell type. These findings establish an important role for K channels in cECs and pericytes in the regulation of CBF.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9623876PMC
http://dx.doi.org/10.1126/scisignal.abl5405DOI Listing

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