{"id":"2d3995b0-4d32-536a-9b40-02f7413bef18","stable_key":"5102beb6-9f61-500e-af10-9ac63649e0b7:renal-native-low-k-requires-chloride-flux","predicate":"lower-extracellular-concentration-increases","statement":"In native mouse kidney preparations, low extracellular K increased NCC phosphorylation through chloride-conductance-dependent SPAK/OSR1 signaling.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"79dbb4c8-82ad-598a-b040-6c6fca2e5646","mechanism_event_label":"The low-potassium signal needs chloride movement to increase the transporter phosphate signal.","subject":{"id":"5dd31e52-f51e-51f3-880e-240abcc0ab1d","slug":"potassium-ion","display_name":"Potassium ion","entity_type_key":"ion"},"object":{"id":"8197e69c-215b-5cd4-bf4b-edde6708ea8f","slug":"ncc-phosphorylation","display_name":"NCC phosphorylation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"79dbb4c8-82ad-598a-b040-6c6fca2e5646","stable_key":"5102beb6-9f61-500e-af10-9ac63649e0b7:renal-native-low-k-requires-chloride-flux-event","event_type":"biochemical_relationship","label":"The low-potassium signal needs chloride movement to increase the transporter phosphate signal.","description":"In native mouse kidney preparations, low extracellular K increased NCC phosphorylation through chloride-conductance-dependent SPAK/OSR1 signaling.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5dd31e52-f51e-51f3-880e-240abcc0ab1d","slug":"potassium-ion","display_name":"Potassium ion","entity_type_key":"ion"},"role":"causal-subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8197e69c-215b-5cd4-bf4b-edde6708ea8f","slug":"ncc-phosphorylation","display_name":"NCC phosphorylation","entity_type_key":"cellular_process"},"role":"measured-target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6f35aa38-f875-5759-b749-97a2f6480ff3","slug":"chloride-ion","display_name":"Chloride ion","entity_type_key":"ion"},"role":"signaling-ion","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6ac31e68-8970-5167-aca8-4ce8d90a66cc","slug":"stk39","display_name":"STE20/SPS1-related proline/alanine-rich kinase","entity_type_key":"protein"},"role":"relay","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"479d0d26-c4f7-596c-bb1b-ebc5163d6f9f","slug":"oxsr1","display_name":"Oxidative stress responsive kinase 1","entity_type_key":"protein"},"role":"relay","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"63291643-1df9-5547-952a-9082838a350e","slug":"slc12a3","display_name":"Thiazide-sensitive sodium-chloride cotransporter","entity_type_key":"protein"},"role":"transporter","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"K concentration regulates sodium/chloride transport via chloride-sensitive signaling.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Abstract and Results; low chloride and DIDS comparisons.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Perfused kidney and kidney slices","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Acute bath/perfusate manipulation is not whole-body potassium depletion.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Potassium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"potassium","display_name":"Potassium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The low-potassium signal needs chloride movement to increase the transporter phosphate signal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Native DCT","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"690cbafc-8984-59e0-b114-fb5b1c3896a5","evidence_kind":"source_excerpt","locator":"Lines 216-227","start_line":216,"end_line":227,"excerpt":"### renal-native-low-k-requires-chloride-flux\nIn native mouse kidney preparations, low extracellular K increased NCC phosphorylation through chloride-conductance-dependent SPAK/OSR1 signaling.\nCondition category: normal\nnutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The low-potassium signal needs chloride movement to increase the transporter phosphate signal.\norganism: Mus musculus\ntissue_or_cell_type: Native DCT\nexperimental_model: Perfused kidney and kidney slices\nlimitations: Acute bath/perfusate manipulation is not whole-body potassium depletion.\ncross_nutrient: K concentration regulates sodium/chloride transport via chloride-sensitive signaling.\nevidence_location: Abstract and Results; low chloride and DIDS comparisons.\n[penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504","model_system":"Perfused kidney and kidney slices","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"241226ee-6b7d-5cc7-9781-e6beb8ee1982","stable_key":"import-5102beb6-9f61-500e-af10-9ac63649e0b7","title":"Potassium: 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":"a8f89f8d84b48c0f93048dfc45f7f57a67dd9a7249968a096a14aeb03d8b7a52","revision_id":"de4ec6f4-58a1-537b-8169-97b783898df1","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}