{"doi":"10.3390/ijms26062654","title":"Activation of Smooth Muscle Kir2.1 Channels and Na+/K+-ATPase Mediates Dilation of Porcine Coronary Arterioles at Physiological Levels of Potassium","abstract":"Metabolic stress on the heart can cause dilation of coronary arterioles for blood flow recruitment. Although potassium ions (K+) released from the myocardium are a major mediator for this response, the underlying signaling pathways for vasodilation are incompletely understood. Herein, the roles of smooth muscle inward-rectifier K+ channel subtype 2.1 (Kir2.1) and Na+/K+-ATPase were examined. Porcine coronary arterioles were isolated, cannulated, and pressurized for vasomotor study. Vessels developed basal tone and dilated concentration-dependently to extraluminal K+ from 7 to 20 mM. Higher K+ concentrations (25–40 mM) caused graded vasoconstriction. Vasodilation to K+ (10 mM) was not altered by endothelial removal, and blockade of ATP-sensitive K+ channels, voltage-sensitive K+ channels, or calcium-activated K+ channels did not affect K+-induced vasodilation. However, sustained but not abrupt transient vasodilation to K+ was reduced by the nonspecific Kir channel inhibitor Ba2+ or Kir2.1 channel blocker chloroethylclonidine. The Na+/K+-ATPase inhibitor ouabain attenuated K+-elicited vasodilation, and ouabain with Ba2+ abolished the response. Transfection of arterioles with Kir2.1 antisense oligonucleotides abolished sustained but not transient dilation. It is concluded that extraluminal K+ elevation within the physiological range induces initial transient dilation of porcine coronary arterioles by activating smooth muscle Na+/K+-ATPase and sustained dilation via smooth muscle Kir2.1 channels.","journal":"International Journal of Molecular Sciences","year":2025,"id":531202,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1411472,"name":"Habib Moshref Razavi","orcid":"0000-0002-1374-5963","position":1,"is_corresponding":false},{"id":1411473,"name":"Xin Xu","orcid":"0000-0003-4611-8170","position":2,"is_corresponding":false},{"id":1336200,"name":"Sonal Somvanshi","orcid":null,"position":3,"is_corresponding":false},{"id":488825,"name":"Mariappan Muthuchamy","orcid":"0000-0002-5572-8563","position":4,"is_corresponding":false},{"id":1411474,"name":"Lih Kuo","orcid":"0000-0002-4912-6910","position":5,"is_corresponding":false},{"id":1411954,"name":"Travis W. Hein","orcid":null,"position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:51:14.579161Z","pmid":"40141296","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":[]}