{"doi":"10.1242/dmm.043885","title":"L-type voltage-gated calcium channel agonists mitigate hearing loss and modify ribbon synapse morphology in the zebrafish model of Usher syndrome type 1","abstract":"ABSTRACT The mariner (myo7aa−/−) mutant is a zebrafish model for Usher syndrome type 1 (USH1). To further characterize hair cell synaptic elements in myo7aa−/− mutants, we focused on the ribbon synapse and evaluated ultrastructure, number and distribution of immunolabeled ribbons, and postsynaptic densities. By transmission electron microscopy, we determined that myo7aa−/− zebrafish have fewer glutamatergic vesicles tethered to ribbon synapses, yet maintain a comparable ribbon area. In myo7aa−/− hair cells, immunolocalization of Ctbp2 showed fewer ribbon-containing cells in total and an altered distribution of Ctbp2 puncta compared to wild-type hair cells. myo7aa−/− mutants have fewer postsynaptic densities – as assessed by MAGUK immunolabeling – compared to wild-type zebrafish. We quantified the circular swimming behavior of myo7aa−/− mutant fish and measured a greater turning angle (absolute smooth orientation). It has previously been shown that L-type voltage-gated calcium channels are necessary for ribbon localization and occurrence of postsynaptic density; thus, we hypothesized and observed that L-type voltage-gated calcium channel agonists change behavioral and synaptic phenotypes in myo7aa−/− mutants in a drug-specific manner. Our results indicate that treatment with L-type voltage-gated calcium channel agonists alter hair cell synaptic elements and improve behavioral phenotypes of myo7aa−/− mutants. Our data support that L-type voltage-gated calcium channel agonists induce morphological changes at the ribbon synapse – in both the number of tethered vesicles and regarding the distribution of Ctbp2 puncta – shift swimming behavior and improve acoustic startle response.","journal":"Disease Models & Mechanisms","year":2020,"id":88597,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9458,"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":449119,"name":"Joseph Dugdale","orcid":"0000-0002-4324-7658","position":1,"is_corresponding":false},{"id":450173,"name":"Trace A. Christenson","orcid":null,"position":2,"is_corresponding":false},{"id":450174,"name":"Jeffrey L. Bellah","orcid":null,"position":3,"is_corresponding":false},{"id":450175,"name":"Aaron Lambert","orcid":null,"position":4,"is_corresponding":false},{"id":449120,"name":"Mark A. Masino","orcid":"0000-0001-9046-8659","position":5,"is_corresponding":false},{"id":254326,"name":"Stephen C. Ekker","orcid":"0000-0003-0726-4212","position":6,"is_corresponding":false},{"id":413663,"name":"Lisa A. Schimmenti","orcid":"0000-0003-3154-4249","position":7,"is_corresponding":false},{"id":449118,"name":"Alaa Koleilat","orcid":"0000-0001-7949-7205","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-18T22:01:22.387926Z","pmid":"33361086","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":[]}