{"doi":"10.1113/jphysiol.2006.112748","title":"The N‐terminal transmembrane domain (TMD0) and a cytosolic linker (L0) of sulphonylurea receptor define the unique intrinsic gating of K<sub>ATP</sub> channels","abstract":"<jats:p>ATP‐sensitive potassium (K<jats:sub>ATP</jats:sub>) channels comprise four pore‐forming Kir6 and four regulatory sulphonylurea receptor (SUR) subunits. SUR, an ATP‐binding cassette protein, associates with Kir6 through its N‐terminal transmembrane domain (TMD0). TMD0 connects to the core domain of SUR through a cytosolic linker (L0). The intrinsic gating of Kir6.2 is greatly altered by SUR. It has been hypothesized that these changes are conferred by TMD0. Exploiting the fact that the pancreatic (SUR1/Kir6.2) and the cardiac (SUR2A/Kir6.2) K<jats:sub>ATP</jats:sub> channels show different gating behaviours, we have tested this hypothesis by comparing the intrinsic gating of Kir6.2 with the last 26 residues deleted (Kir6.2Δ26) co‐expressed with SUR1, S1‐TMD0, SUR2A and S2‐TMD0 at −40 and −100 mV (S is an abbreviation for SUR; TMD0/Kir6.2Δ26, but not TMD0/Kir6.2, can exit the endoplastic reticulum and reach the cell membrane). Single‐channel kinetic analyses revealed that the mean burst and interburst durations are shorter for TMD0/Kir6.2Δ26 than for the corresponding SUR channels. No differences were found between the two TMD0 channels. We further demonstrated that in isolation even TMD0‐L0 (SUR truncated after L0) cannot confer the wild‐type intrinsic gating to Kir6.2Δ26 and that swapping L0 (SUR truncated after L0)between SUR1 and SUR2A only partially exchanges their different intrinsic gating. Therefore, in addition to TMD0, L0 and the core domain also participate in determining the intrinsic gating of Kir6.2. However, TMD0 and L0 are responsible for the different gating patterns of full‐length SUR1 and SUR2A channels. A kinetic model with one open and four closed states is presented to explain our results in a mechanistic context.</jats:p>","journal":"The Journal of Physiology","year":2006,"id":679359,"datarank":0.5456379239589579,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"self_citation_contribution":0.5456379239589579,"citation_network_contribution":0.0,"self_endowment_contribution":0.5456379239589579,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1753686,"name":"László Csanády","orcid":null,"position":1,"is_corresponding":false},{"id":1753685,"name":"Kim W. Chan","orcid":null,"position":2,"is_corresponding":false},{"id":503627,"name":"Kun Fang","orcid":"0000-0002-2569-8543","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The N‐terminal transmembrane domain (TMD0) and a cytosolic linker (L0) of sulphonylurea receptor define the unique intrinsic gating of K<sub>ATP</sub> channels","abstract":"<jats:p>ATP‐sensitive potassium (K<jats:sub>ATP</jats:sub>) channels comprise four pore‐forming Kir6 and four regulatory sulphonylurea receptor (SUR) subunits. SUR, an ATP‐binding cassette protein, associates with Kir6 through its N‐terminal transmembrane domain (TMD0). TMD0 connects to the core domain of SUR through a cytosolic linker (L0). The intrinsic gating of Kir6.2 is greatly altered by SUR. It has been hypothesized that these changes are conferred by TMD0. Exploiting the fact that the pancreatic (SUR1/Kir6.2) and the cardiac (SUR2A/Kir6.2) K<jats:sub>ATP</jats:sub> channels show different gating behaviours, we have tested this hypothesis by comparing the intrinsic gating of Kir6.2 with the last 26 residues deleted (Kir6.2Δ26) co‐expressed with SUR1, S1‐TMD0, SUR2A and S2‐TMD0 at −40 and −100 mV (S is an abbreviation for SUR; TMD0/Kir6.2Δ26, but not TMD0/Kir6.2, can exit the endoplastic reticulum and reach the cell membrane). Single‐channel kinetic analyses revealed that the mean burst and interburst durations are shorter for TMD0/Kir6.2Δ26 than for the corresponding SUR channels. No differences were found between the two TMD0 channels. We further demonstrated that in isolation even TMD0‐L0 (SUR truncated after L0) cannot confer the wild‐type intrinsic gating to Kir6.2Δ26 and that swapping L0 (SUR truncated after L0)between SUR1 and SUR2A only partially exchanges their different intrinsic gating. Therefore, in addition to TMD0, L0 and the core domain also participate in determining the intrinsic gating of Kir6.2. However, TMD0 and L0 are responsible for the different gating patterns of full‐length SUR1 and SUR2A channels. A kinetic model with one open and four closed states is presented to explain our results in a mechanistic context.</jats:p>","is_dataset_classified":null,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16887879","pmcid":null,"openalex_id":"https://openalex.org/W1556366471","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK060104","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK60104","title":null}],"total_grants":2,"fwci":2.3126,"citation_percentile":0.87775906,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2014,"count":1},{"year":2015,"count":4},{"year":2016,"count":1},{"year":2017,"count":3},{"year":2018,"count":3},{"year":2019,"count":2},{"year":2020,"count":1},{"year":2022,"count":2}],"oa_status":"green","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1890349","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1890349","host_type":"repository"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1113%2Fjphysiol.2006.112748","host_type":"publisher"},{"url":"https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.2006.112748","host_type":"publisher"},{"url":"https://doi.org/10.1113/jphysiol.2006.112748","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16887879","host_type":"repository"}],"fields_of_study":["Cardiac Ischemia and Reperfusion","Ion channel regulation and function","Mechanical Circulatory Support Devices","ATP-Binding Cassette Transporters","Animals","Cells, Cultured","Chimera","Cricetinae","Electrophysiology","Female","Ion Channel Gating","Membrane Potentials","Mice","Patch-Clamp Techniques","Potassium Channels","Potassium Channels, Inwardly Rectifying","Protein Structure, Tertiary","Protein Subunits","Rats","Receptors, Drug","Sulfonylurea Receptors","Xenopus laevis","Kcnj11 Channel"],"mesh_terms":["Kcnj11 Channel","Animals","Cells, Cultured","Chimera","Electrophysiology","Female","Cricetinae","Membrane Potentials","Receptors, Drug","Xenopus laevis","Potassium Channels","Ion Channel Gating","Protein Structure, Tertiary","Patch-Clamp Techniques","ATP-Binding Cassette Transporters","Protein Subunits","Potassium Channels, Inwardly Rectifying","Mice","Rats","Sulfonylurea Receptors"],"keywords":["Gating","Kir6.2","Biophysics","Sulfonylurea receptor","Transmembrane domain","Chemistry","Potassium channel","Transmembrane protein","Linker","Cytosol","Transmembrane channels","Biochemistry","Cell biology","Ion channel","Receptor","Voltage-gated ion channel","Biology","Protein subunit","Enzyme","Computer science"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T13:00:10.975846Z","pmid":null,"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":[]}