{"doi":"10.1152/physrev.00013.2022","title":"Ion channels and channelopathies in glomeruli","abstract":"<jats:p>An essential step in renal function entails the formation of an ultrafiltrate that is delivered to the renal tubules for subsequent processing. This process, known as glomerular filtration, is controlled by intrinsic regulatory systems and by paracrine, neuronal, and endocrine signals that converge onto glomerular cells. In addition, the characteristics of glomerular fluid flow, such as the glomerular filtration rate and the glomerular filtration fraction, play an important role in determining blood flow to the rest of the kidney. Consequently, disease processes that initially affect glomeruli are the most likely to lead to end-stage kidney failure. The cells that comprise the glomerular filter, especially podocytes and mesangial cells, express many different types of ion channels that regulate intrinsic aspects of cell function and cellular responses to the local environment, such as changes in glomerular capillary pressure. Dysregulation of glomerular ion channels, such as changes in TRPC6, can lead to devastating glomerular diseases, and a number of channels, including TRPC6, TRPC5, and various ionotropic receptors, are promising targets for drug development. This review discusses glomerular structure and glomerular disease processes. It also describes the types of plasma membrane ion channels that have been identified in glomerular cells, the physiological and pathophysiological contexts in which they operate, and the pathways by which they are regulated and dysregulated. The contributions of these channels to glomerular disease processes, such as focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, as well as the development of drugs that target these channels are also discussed.</jats:p>","journal":"Physiological Reviews","year":2023,"id":656170,"datarank":0.6681520944380261,"base_score":4.454347296253507,"endowment":4.454347296253507,"self_citation_contribution":0.6681520944380261,"citation_network_contribution":0.0,"self_endowment_contribution":0.6681520944380261,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":85,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":687716,"name":"Rong Ma","orcid":"0000-0002-5896-9178","position":1,"is_corresponding":false},{"id":364384,"name":"Oleg Palygin","orcid":"0000-0002-3680-5527","position":2,"is_corresponding":false},{"id":710577,"name":"Stuart E. Dryer","orcid":"0000-0003-4265-104X","position":3,"is_corresponding":false},{"id":364390,"name":"Alexander Staruschenko","orcid":"0000-0002-5190-8356","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Ion channels and channelopathies in glomeruli","abstract":"<jats:p>An essential step in renal function entails the formation of an ultrafiltrate that is delivered to the renal tubules for subsequent processing. This process, known as glomerular filtration, is controlled by intrinsic regulatory systems and by paracrine, neuronal, and endocrine signals that converge onto glomerular cells. In addition, the characteristics of glomerular fluid flow, such as the glomerular filtration rate and the glomerular filtration fraction, play an important role in determining blood flow to the rest of the kidney. Consequently, disease processes that initially affect glomeruli are the most likely to lead to end-stage kidney failure. The cells that comprise the glomerular filter, especially podocytes and mesangial cells, express many different types of ion channels that regulate intrinsic aspects of cell function and cellular responses to the local environment, such as changes in glomerular capillary pressure. Dysregulation of glomerular ion channels, such as changes in TRPC6, can lead to devastating glomerular diseases, and a number of channels, including TRPC6, TRPC5, and various ionotropic receptors, are promising targets for drug development. This review discusses glomerular structure and glomerular disease processes. It also describes the types of plasma membrane ion channels that have been identified in glomerular cells, the physiological and pathophysiological contexts in which they operate, and the pathways by which they are regulated and dysregulated. The contributions of these channels to glomerular disease processes, such as focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, as well as the development of drugs that target these channels are also discussed.</jats:p>","is_dataset_classified":null,"base_score":4.454347296253507,"endowment":4.454347296253507,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36007181","pmcid":"PMC9662803","openalex_id":"https://openalex.org/W4293094820","authors":[],"funders":[{"funder_name":"HHS | NIH | National Heart, Lung, and Blood Institute","grant_id":"R35 HL135749","title":null},{"funder_name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","grant_id":"R21 DK129882","title":null},{"funder_name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","grant_id":"R01 DK126720","title":null},{"funder_name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","grant_id":"R01 DK104708","title":null},{"funder_name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","grant_id":"R01 DK115424","title":null},{"funder_name":"U.S. Department of Veterans Affairs","grant_id":"I01 BX004024","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK129227","title":null}],"total_grants":7,"fwci":9.1672,"citation_percentile":0.992287,"influential_citations":0,"citation_trend":[{"year":2022,"count":2},{"year":2023,"count":30},{"year":2024,"count":17},{"year":2025,"count":29},{"year":2026,"count":7}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9662803","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9662803","host_type":"repository"},{"url":"https://journals.physiology.org/doi/pdf/10.1152/physrev.00013.2022","host_type":"publisher"},{"url":"https://doi.org/10.1152/physrev.00013.2022","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36007181","host_type":"repository"}],"fields_of_study":["Ion Channels and Receptors","Ion Transport and Channel Regulation","Renal Diseases and Glomerulopathies"],"mesh_terms":["TRPC6 Cation Channel","Glomerulosclerosis, Focal Segmental","Humans","Kidney Diseases","Kidney Glomerulus","TRPC Cation Channels","Channelopathies"],"keywords":["Podocyte","Renal function","Renal blood flow","Glomerulosclerosis","Renal glomerulus","Diabetic nephropathy","Focal segmental glomerulosclerosis","Chemistry","Internal medicine","Kidney","Endocrinology","Filtration fraction","Biology","Medicine","Glomerulonephritis","Proteinuria","NMDA receptors","glomerular filtration rate","Trpc Channels","Store-operated Calcium Channels","Kca1.1 Channels"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T20:02:25.086706Z","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":[]}