{"doi":"10.7554/elife.79648","title":"α1-Adrenergic receptor–PKC–Pyk2–Src signaling boosts L-type Ca2+ channel CaV1.2 activity and long-term potentiation in rodents","abstract":"The cellular mechanisms mediating norepinephrine (NE) functions in brain to result in behaviors are unknown. We identified the L-type Ca 2+ channel (LTCC) Ca V 1.2 as a principal target for G q -coupled α 1 -adrenergic receptors (ARs). α 1 AR signaling increased LTCC activity in hippocampal neurons. This regulation required protein kinase C (PKC)-mediated activation of the tyrosine kinases Pyk2 and, downstream, Src. Pyk2 and Src were associated with Ca V 1.2. In model neuroendocrine PC12 cells, stimulation of PKC induced tyrosine phosphorylation of Ca V 1.2, a modification abrogated by inhibition of Pyk2 and Src. Upregulation of LTCC activity by α 1 AR and formation of a signaling complex with PKC, Pyk2, and Src suggests that Ca V 1.2 is a central conduit for signaling by NE. Indeed, a form of hippocampal long-term potentiation (LTP) in young mice requires both the LTCC and α 1 AR stimulation. Inhibition of Pyk2 and Src blocked this LTP, indicating that enhancement of Ca V 1.2 activity via α 1 AR–Pyk2–Src signaling regulates synaptic strength.","journal":"eLife","year":2023,"id":344546,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":355957,"name":"Peter H. Bartels","orcid":"0000-0001-5852-1835","position":1,"is_corresponding":false},{"id":482646,"name":"Peter B. Henderson","orcid":"0000-0002-9407-4371","position":2,"is_corresponding":false},{"id":282996,"name":"Karam Kim","orcid":"0000-0002-1886-5163","position":3,"is_corresponding":false},{"id":1083353,"name":"Mei Shi","orcid":null,"position":4,"is_corresponding":false},{"id":1082981,"name":"Mingxu Zhang","orcid":"0000-0003-3683-2661","position":5,"is_corresponding":false},{"id":1082982,"name":"Sheng‐Yang Ho","orcid":"0009-0000-2292-6494","position":6,"is_corresponding":false},{"id":316555,"name":"Madeline Nieves‐Cintrón","orcid":"0000-0003-1935-8400","position":7,"is_corresponding":false},{"id":304912,"name":"Manuel F. Navedo","orcid":"0000-0001-6864-6594","position":8,"is_corresponding":false},{"id":482648,"name":"Mary C. Horne","orcid":"0000-0002-2799-3212","position":9,"is_corresponding":false},{"id":355959,"name":"Johannes Hell","orcid":"0000-0001-7960-7531","position":10,"is_corresponding":false},{"id":482647,"name":"Kwun Nok Mimi Man","orcid":"0000-0002-0132-9129","position":0,"is_corresponding":true}],"reference_count":147,"raw_metadata":null,"created_at":"2026-07-19T01:11:30.951510Z","pmid":"37338965","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":[]}