{"doi":"10.1113/jp286859","title":"Spine apparatus modulates Ca<sup>2+</sup> in spines through spatial localization of sources and sinks","abstract":"Abstract Dendritic spines are small protrusions on dendrites in neurons and serve as sites of postsynaptic activity. Some of these spines contain smooth endoplasmic reticulum (SER), and sometimes an even further specialized SER known as the spine apparatus (SA). In this work we developed a stochastic spatial model to investigate the role of the SER and the SA in modulating Ca 2+ dynamics. Using this model, we investigated how ryanodine receptor (RyR) localization, IP 3 R localization, spine membrane geometry and SER geometry can impact Ca 2+ transients in the spine and in the dendrite. Our simulations found that RyR opening is dependent on its location in the SER and on the SER geometry. To maximize Ca 2+ in the dendrites (for activating clusters of spines and spine‐to‐spine communication), a laminar SA was favourable with RyRs localized in the neck region, closer to the dendrite. Furthermore locating the IP 3 Rs in the dendrite, as measured experimentally, also increases Ca 2+ in the dendrite. We also found that the presence of the SER without the laminar structure, coupled with RyR localization at the head, leads to higher Ca 2+ presence in the spine. These predictions serve as design principles for understanding how spines with an ER can regulate Ca 2+ dynamics differently from spines without ER through a combination of geometry and receptor localization. image Key points Ca 2+ transients in the spine are characterized by the interplay among membrane receptors, RyRs, SERCA, and IP 3 Rs. Here we build a spatial, particle‐based stochastic model that integrates these components to study how the spine apparatus and receptor localization affect Ca 2+ signaling. Our results show that positioning RyRs near the neck of the spine apparatus enhances spine‐to‐dendrite communication. Additionally, our model highlights the importance of membrane curvature and spine apparatus shape for Ca 2+ signaling within dendritic spines.","journal":"The Journal of Physiology","year":2025,"id":553867,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":683639,"name":"Guadalupe C. García","orcid":"0000-0002-2227-2483","position":1,"is_corresponding":false},{"id":494511,"name":"Frédéric J. Hoerndli","orcid":"0000-0001-6838-0386","position":2,"is_corresponding":false},{"id":432342,"name":"Kimberly J. McCabe","orcid":"0000-0001-9153-8313","position":3,"is_corresponding":false},{"id":232970,"name":"Padmini Rangamani","orcid":"0000-0001-5953-4347","position":4,"is_corresponding":false},{"id":1167738,"name":"María Hernández Mesa","orcid":"0000-0002-9386-9578","position":0,"is_corresponding":true}],"reference_count":113,"raw_metadata":null,"created_at":"2026-07-19T02:54:45.872391Z","pmid":"40817885","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":[]}