{"doi":"10.1101/2021.03.12.435152","title":"Electro-Metabolic Sensing Through Capillary ATP-Sensitive K <sup>+</sup> Channels and Adenosine to Control Cerebral Blood Flow","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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":217284,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":458958,"name":"Nicholas R. Klug","orcid":"0000-0001-7540-0306","position":1,"is_corresponding":false},{"id":649935,"name":"Amreen Mughal","orcid":"0000-0002-0046-2286","position":2,"is_corresponding":false},{"id":814103,"name":"Thomas J. Heppner","orcid":"0000-0001-8052-7192","position":3,"is_corresponding":false},{"id":300695,"name":"David C. Hill‐Eubanks","orcid":"0000-0002-6866-1863","position":4,"is_corresponding":false},{"id":300696,"name":"Mark T. Nelson","orcid":"0000-0002-6608-8784","position":5,"is_corresponding":false},{"id":720873,"name":"María Sancho","orcid":"0000-0003-4750-1040","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T23:53:20.374789Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}