{"doi":"10.7554/elife.94908","title":"A non-conducting role of the Cav1.4 Ca2+ channel drives homeostatic plasticity at the cone photoreceptor synapse","abstract":"In congenital stationary night blindness, type 2 (CSNB2)—a disorder involving the Ca v 1.4 (L-type) Ca 2+ channel—visual impairment is mild considering that Ca v 1.4 mediates synaptic release from rod and cone photoreceptors. Here, we addressed this conundrum using a Ca v 1.4 knockout (KO) mouse and a knock-in (G369i KI) mouse expressing a non-conducting Ca v 1.4. Surprisingly, Ca v 3 (T-type) Ca 2+ currents were detected in cones of G369i KI mice and Ca v 1.4 KO mice but not in cones of wild-type mouse, ground squirrels, and macaque retina. Whereas Ca v 1.4 KO mice are blind, G369i KI mice exhibit normal photopic (i.e. cone-mediated) visual behavior. Cone synapses, which fail to form in Ca v 1.4 KO mice, are present, albeit enlarged, and with some errors in postsynaptic wiring in G369i KI mice. While Ca v 1.4 KO mice lack evidence of cone synaptic responses, electrophysiological recordings in G369i KI mice revealed nominal transmission from cones to horizontal cells and bipolar cells. In CSNB2, we propose that Ca v 3 channels maintain cone synaptic output provided that the nonconducting role of Ca v 1.4 in cone synaptogenesis remains intact. Our findings reveal an unexpected form of homeostatic plasticity that relies on a non-canonical role of an ion channel.","journal":"eLife","year":2024,"id":484802,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":721650,"name":"Gregory J. Ordemann","orcid":"0000-0001-9755-7312","position":1,"is_corresponding":false},{"id":1316499,"name":"Juan AM de la Rosa Vázquez","orcid":null,"position":2,"is_corresponding":false},{"id":1196312,"name":"Angie Huang","orcid":"0000-0001-8757-985X","position":3,"is_corresponding":false},{"id":1196313,"name":"Christof Gault","orcid":"0009-0009-6462-9880","position":4,"is_corresponding":false},{"id":1091144,"name":"Serena R. Wisner","orcid":null,"position":5,"is_corresponding":false},{"id":1196314,"name":"Kate Randall","orcid":"0000-0002-7199-9806","position":6,"is_corresponding":false},{"id":1073832,"name":"Daiki Futagi","orcid":"0000-0003-3972-2054","position":7,"is_corresponding":false},{"id":417534,"name":"Nihal A. Salem","orcid":"0000-0001-9973-6437","position":8,"is_corresponding":false},{"id":1316500,"name":"Dayne Mayfield","orcid":null,"position":9,"is_corresponding":false},{"id":386026,"name":"Boris V. Zemelman","orcid":"0000-0003-2463-4887","position":10,"is_corresponding":false},{"id":1073834,"name":"Steven H. DeVries","orcid":"0000-0002-9636-4196","position":11,"is_corresponding":false},{"id":460681,"name":"Mrinalini Hoon","orcid":"0000-0002-3590-8743","position":12,"is_corresponding":false},{"id":607694,"name":"Amy Lee","orcid":"0000-0001-8021-0443","position":13,"is_corresponding":false},{"id":892757,"name":"J. Wesley Maddox","orcid":"0000-0002-1630-2746","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-19T02:07:42.971417Z","pmid":"39531384","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":[]}