{"id":"ef1723d4-5c36-5c61-9927-da667c6edbe9","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:cav12-ef-hand-magnesium-sensitivity","predicate":"alters","statement":"CaV1.2 EF-hand substitutions shifted Mg inhibition, with D1546K eliminating sensitivity across the tested range.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"6bbdae70-fcad-508c-8e96-dd681f7e5225","mechanism_event_label":"Changing the channel regulatory site changed its response to intracellular magnesium.","subject":{"id":"16e2a21d-b92e-5b8c-b337-4a0d1de65982","slug":"cav1-2-ef-hand-mutants","display_name":"CaV1.2 EF-hand mutants tested by Brunet et al.","entity_type_key":"protein_set"},"object":{"id":"db0060cf-33fb-5d8d-9fda-7955fd5f6386","slug":"cav1-2-current","display_name":"CaV1.2-mediated ionic current","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"6bbdae70-fcad-508c-8e96-dd681f7e5225","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:cav12-ef-hand-magnesium-sensitivity-event","event_type":"biochemical_relationship","label":"Changing the channel regulatory site changed its response to intracellular magnesium.","description":"CaV1.2 EF-hand substitutions shifted Mg inhibition, with D1546K eliminating sensitivity across the tested range.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"223bef0d-65dc-5dbb-8db3-c0792622e2e9","slug":"cacna1c","display_name":"CaV1.2 alpha1C / CACNA1C","entity_type_key":"protein"},"role":"wild-type-reference","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"bff427ab-35f9-59c2-bb24-fd5953bbaec2","slug":"magnesium-ion","display_name":"Mg2+","entity_type_key":"ion"},"role":"regulator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"permeant-ion","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"16e2a21d-b92e-5b8c-b337-4a0d1de65982","slug":"cav1-2-ef-hand-mutants","display_name":"CaV1.2 EF-hand mutants tested by Brunet et al.","entity_type_key":"protein_set"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"db0060cf-33fb-5d8d-9fda-7955fd5f6386","slug":"cav1-2-current","display_name":"CaV1.2-mediated ionic current","entity_type_key":"cellular_process"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"The regulatory protein site connects intracellular magnesium with calcium-channel current.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence-system","value_text":"EF-hand mutagenesis and patch clamp; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"EF-hand mutagenesis and patch clamp; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Calculated intracellular free Mg was varied over 0.1-7.2 mM, with a 0.8 mM control; pipette MgATP was held at 5 mM. Ca2+ or Ba2+ served as the permeant ion in separate recordings.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Supports an EF-hand-associated regulatory mechanism; not direct structural observation of bound Mg.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Magnesium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"magnesium","display_name":"Magnesium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Rabbit cardiac CaV1.2 protein expressed in human-derived tsA-201 cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Changing the channel regulatory site changed its response to intracellular magnesium.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[brunet-2005-cav12] Modulation of CaV1.2 channels by Mg2+ acting at an EF-hand motif in the COOH-terminal domain (2005). https://pmc.ncbi.nlm.nih.gov/articles/PMC2266622/ DOI: 10.1085/jgp.200509333","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"tsA-201 cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"tsA-201 cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"e6c8f85a-1ede-599c-a35c-7ba04643a672","evidence_kind":"source_excerpt","locator":"Lines 1303-1316","start_line":1303,"end_line":1316,"excerpt":"### cav12-ef-hand-magnesium-sensitivity\nCaV1.2 EF-hand substitutions shifted Mg inhibition, with D1546K eliminating sensitivity across the tested range.\nCondition category: machinery_impairment\nnutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Changing the channel regulatory site changed its response to intracellular magnesium.\norganism: Rabbit cardiac CaV1.2 protein expressed in human-derived tsA-201 cells\ntissue_or_cell_type: tsA-201 cells\nexperimental_model: EF-hand mutagenesis and patch clamp; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits\nlimitations: Supports an EF-hand-associated regulatory mechanism; not direct structural observation of bound Mg.\ncross_nutrient: The regulatory protein site connects intracellular magnesium with calcium-channel current.\nexposure: Calculated intracellular free Mg was varied over 0.1-7.2 mM, with a 0.8 mM control; pipette MgATP was held at 5 mM. Ca2+ or Ba2+ served as the permeant ion in separate recordings.\nevidence-system: EF-hand mutagenesis and patch clamp; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits\ntissue: tsA-201 cells\n[brunet-2005-cav12] Modulation of CaV1.2 channels by Mg2+ acting at an EF-hand motif in the COOH-terminal domain (2005). https://pmc.ncbi.nlm.nih.gov/articles/PMC2266622/ DOI: 10.1085/jgp.200509333","model_system":"EF-hand mutagenesis and patch clamp; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [brunet-2005-cav12] Modulation of CaV1.2 channels by Mg2+ acting at an EF-hand motif in the COOH-terminal domain (2005). https://pmc.ncbi.nlm.nih.gov/articles/PMC2266622/ DOI: 10.1085/jgp.200509333","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"dd101e28-1a2e-5a48-9d1e-809c77514866","stable_key":"import-0f17db03-207f-5910-ac8e-13dfc2f378ce","title":"Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"e111c412f57143a17e8e65e74e8f7888b5bb9a61099873f4767f527fac19bb07","revision_id":"6b7f04f2-66ed-5859-955f-c2b50d4bf041","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}