{"doi":"10.1101/2023.06.27.546725","title":"The formation of K <sub>V</sub> 2.1 macro-clusters is required for sex-specific differences in L-type Ca <sub>V</sub> 1.2 clustering and function in arterial myocytes","abstract":"Abstract In arterial myocytes, the canonical function of voltage-gated Ca V 1.2 and K V 2.1 channels is to induce myocyte contraction and relaxation through their responses to membrane depolarization, respectively. Paradoxically, K V 2.1 also plays a sex-specific role by promoting the clustering and activity of Ca V 1.2 channels. However, the impact of K V 2.1 protein organization on Ca V 1.2 function remains poorly understood. We discovered that K V 2.1 forms micro-clusters, which can transform into large macro-clusters when a critical clustering site (S590) in the channel is phosphorylated in arterial myocytes. Notably, female myocytes exhibit greater phosphorylation of S590, and macro-cluster formation compared to males. Contrary to current models, the activity of K V 2.1 channels seems unrelated to density or macro-clustering in arterial myocytes. Disrupting the K V 2.1 clustering site (K V 2.1 S590A ) eliminated K V 2.1 macro-clustering and sex-specific differences in Ca V 1.2 cluster size and activity. We propose that the degree of K V 2.1 clustering tunes Ca V 1.2 channel function in a sex-specific manner in arterial myocytes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":409111,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":458954,"name":"Samantha C. O’Dwyer","orcid":"0000-0001-5334-9984","position":1,"is_corresponding":false},{"id":953056,"name":"Declan Manning","orcid":"0009-0001-4107-4829","position":2,"is_corresponding":false},{"id":1077923,"name":"Gonzalo Hernandez-Hernandez","orcid":"0000-0001-6940-9005","position":3,"is_corresponding":false},{"id":1046972,"name":"Paula Rhana","orcid":null,"position":4,"is_corresponding":false},{"id":1077924,"name":"Zhihui Fong","orcid":"0000-0002-0521-0088","position":5,"is_corresponding":false},{"id":692580,"name":"Daisuke Sato","orcid":"0000-0001-9341-0970","position":6,"is_corresponding":false},{"id":294215,"name":"Colleen E. Clancy","orcid":"0000-0001-6849-4885","position":7,"is_corresponding":false},{"id":658544,"name":"Nicholas C. Vierra","orcid":"0000-0001-7269-5399","position":8,"is_corresponding":false},{"id":181300,"name":"James S Trimmer","orcid":"0000-0002-6117-3912","position":9,"is_corresponding":false},{"id":355960,"name":"Luis F. Santana","orcid":"0000-0002-4297-8029","position":10,"is_corresponding":false},{"id":458956,"name":"Collin Matsumoto","orcid":"0000-0002-5370-1156","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:21:22.368387Z","pmid":"37425816","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":[]}