{"doi":"10.1172/jci.insight.132496","title":"Control of PTH secretion by the TRPC1 ion channel","abstract":"Familial hypocalciuric hypercalcemia (FHH) is a genetic condition associated with hypocalciuria, hypercalcemia, and, in some cases, inappropriately high levels of circulating parathyroid hormone (PTH). FHH is associated with inactivating mutations in the gene encoding the Ca2+-sensing receptor (CaSR), a GPCR, and GNA11 encoding G protein subunit α 11 (Gα11), implicating defective GPCR signaling as the root pathophysiology for FHH. However, the downstream mechanism by which CaSR activation inhibits PTH production/secretion is incompletely understood. Here, we show that mice lacking the transient receptor potential canonical channel 1 (TRPC1) develop chronic hypercalcemia, hypocalciuria, and elevated PTH levels, mimicking human FHH. Ex vivo and in vitro studies revealed that TRPC1 serves a necessary and sufficient mediator to suppress PTH secretion from parathyroid glands (PTGs) downstream of CaSR in response to high extracellular Ca2+ concentration. Gα11 physically interacted with both the N- and C-termini of TRPC1 and enhanced CaSR-induced TRPC1 activity in transfected cells. These data identify TRPC1-mediated Ca2+ signaling as an essential component of the cellular apparatus controlling PTH secretion in the PTG downstream of CaSR.","journal":"JCI Insight","year":2020,"id":81024,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"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":421050,"name":"Bonnie Eby","orcid":null,"position":1,"is_corresponding":false},{"id":421051,"name":"Vasyl Nesin","orcid":null,"position":2,"is_corresponding":false},{"id":403774,"name":"Peter Ngo","orcid":null,"position":3,"is_corresponding":false},{"id":408889,"name":"Megan R. Lerner","orcid":"0000-0003-2645-8311","position":4,"is_corresponding":false},{"id":419683,"name":"Caroline M. Gorvin","orcid":"0000-0002-1361-9174","position":5,"is_corresponding":false},{"id":419684,"name":"Victoria Stokes","orcid":"0000-0002-9000-0834","position":6,"is_corresponding":false},{"id":245224,"name":"Rajesh V. Thakker","orcid":"0000-0002-1438-3220","position":7,"is_corresponding":false},{"id":16407,"name":"Maria Luisa Brandi","orcid":"0000-0002-8741-0592","position":8,"is_corresponding":false},{"id":268743,"name":"Wenhan Chang","orcid":"0000-0001-6583-7176","position":9,"is_corresponding":false},{"id":15666,"name":"Mary Beth Humphrey","orcid":"0000-0003-0042-4068","position":10,"is_corresponding":false},{"id":403111,"name":"Leonidas Tsiokas","orcid":"0000-0002-3659-1813","position":11,"is_corresponding":false},{"id":419685,"name":"Kai Lau","orcid":"0009-0002-3378-0560","position":12,"is_corresponding":false},{"id":421049,"name":"Marta Onopiuk","orcid":null,"position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:52:34.401799Z","pmid":"32213715","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":[]}