{"doi":"10.1016/j.bpr.2021.100005","title":"Comparative Ca2+ channel contributions to intracellular Ca2+ levels in the circadian clock","abstract":"Circadian rhythms in mammals are coordinated by the central clock in the brain, located in the suprachiasmatic nucleus (SCN). Multiple molecular and cellular signals display a circadian variation within SCN neurons, including intracellular Ca 2+ , but the mechanisms are not definitively established. SCN cytosolic Ca 2+ levels exhibit a peak during the day, when both action potential firing and Ca 2+ channel activity are increased, and are decreased at night, correlating with a reduction in firing rate. In this study, we employ a single-color fluorescence anisotropy reporter (FLARE), Venus FLARE-Cameleon, and polarization inverted selective-plane illumination microscopy to measure rhythmic changes in cytosolic Ca 2+ in SCN neurons. Using this technique, the Ca 2+ channel subtypes contributing to intracellular Ca 2+ at the peak and trough of the circadian cycle were assessed using a pharmacological approach with Ca 2+ channel inhibitors. Peak (218 ± 16 nM) and trough (172 ± 13 nM) Ca 2+ levels were quantified, indicating a 1.3-fold circadian variance in Ca 2+ concentration. Inhibition of ryanodine-receptor-mediated Ca 2+ release produced a larger relative decrease in cytosolic Ca 2+ at both time points compared to voltage-gated Ca 2+ channels. These results support the hypothesis that circadian Ca 2+ rhythms in SCN neurons are predominantly driven by intracellular Ca 2+ channels, although not exclusively so. The study provides a foundation for future experiments to probe Ca 2+ signaling in a dynamic biological context using FLAREs.","journal":"Biophysical Reports","year":2021,"id":203634,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9428,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":563572,"name":"Vishnu P. Rao","orcid":"0000-0002-4396-1579","position":1,"is_corresponding":false},{"id":563573,"name":"Megan A. Rizzo","orcid":"0000-0001-6528-7768","position":2,"is_corresponding":false},{"id":784920,"name":"Andrea L. Meredith","orcid":"0000-0003-1061-2302","position":3,"is_corresponding":false},{"id":784919,"name":"Amber E. Plante","orcid":"0000-0002-1010-2348","position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":null,"created_at":"2026-07-18T23:51:18.050175Z","pmid":"35330949","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":[]}