{"doi":"10.1073/pnas.2003510117","title":"Metabolic–electrical control of coronary blood flow","abstract":"The heart is a metabolically demanding organ with limited energetic reserves to sustain its monumental workload. An efficient blood supply via the coronary vascular network is therefore critical for maintaining efficient cardiac muscle function. The coronary vascular network originates just above the aortic valve, where the right and left main coronary arteries connect to the ascending aorta. These arteries branch out into smaller-diameter arterioles that connect to capillaries, where oxygen exchange takes place (Fig. 1). In PNAS, Zhao et al. (1) describe a signaling pathway in the heart that couples metabolic changes in ventricular myocytes to hyperpolarization of capillary endothelial cells (cECs). This hyperpolarizing signal rapidly propagates throughout the arteriolar tree, causing vasodilation. The resulting upstream vasodilatory response is necessary to increase blood flow during periods of cardiac muscle metabolic stress to match oxygen supply with metabolic demands. The physiological implications of these findings are described below. Fig. 1. Metabolic–electrical signaling in the coronary vasculature. During resting conditions, cardiomyocytes (CMs) have high levels of intracellular ATP ([ATP]i) and low levels of extracellular K+ ([K+]o). Upon increased myocardial contraction, levels of [ATP]i decrease and [K+]o increases. Decreased [ATP]I levels trigger the activation of KATP channels expressed in the CM plasma membrane. Efflux of K+ ions induces hyperpolarization of CMs. Hyperpolarizing current passes to electrically coupled capillary endothelial cells (cECs) via gap junctions. The hyperpolarizing signal then travels in a retrograde direction along the cEC network to an upstream arteriole. This hyperpolarizing signal induces relaxation of the smooth muscle cells that encapsulate the coronary vasculature. A central tenet in cardiac physiology is that oxygen extraction efficiency is almost at saturation in the coronary circulation (2). Increasing oxygen demand is rapidly matched by increased blood flow via changes in perfusion pressure or vascular … [↵][1]1To whom correspondence may be addressed. Email: lfsantana{at}ucdavis.edu. [1]: #xref-corresp-1-1","journal":"Proceedings of the National Academy of Sciences","year":2020,"id":84503,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":355960,"name":"Luis F. Santana","orcid":"0000-0002-4297-8029","position":1,"is_corresponding":false},{"id":433645,"name":"Nathan Grainger","orcid":"0000-0002-3954-7041","position":0,"is_corresponding":true}],"reference_count":13,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:55:38.506333Z","pmid":"32238556","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":[]}