{"doi":"10.1152/jappl.2001.91.3.1350","title":"β<sub>1</sub>-subunit of BK channels regulates arterial wall [Ca<sup>2+</sup>] and diameter in mouse cerebral arteries","abstract":"<jats:p> Mice with a disrupted β<jats:sub>1</jats:sub>(BKβ<jats:sub>1</jats:sub>)-subunit of the large-conductance Ca<jats:sup>2+</jats:sup>-activated K<jats:sup>+</jats:sup> (BK) channel gene develop systemic hypertension and cardiac hypertrophy, which is likely caused by uncoupling of Ca<jats:sup>2+</jats:sup> sparks to BK channels in arterial smooth muscle cells. However, little is known about the physiological levels of global intracellular Ca<jats:sup>2+</jats:sup> concentration ([Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>) and its regulation by Ca<jats:sup>2+</jats:sup> sparks and BK channel subunits. We utilized a BKβ<jats:sub>1</jats:sub> knockout C57BL/6 mouse model and studied the effects of inhibitors of ryanodine receptor and BK channels on the global [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> and diameter of small cerebral arteries pressurized to 60 mmHg. Ryanodine (10 μM) or iberiotoxin (100 nM) increased [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> by ∼75 nM and constricted +/+ BKβ<jats:sub>1</jats:sub> wild-type arteries (pressurized to 60 mmHg) with myogenic tone by ∼10 μm. In contrast, ryanodine (10 μM) or iberiotoxin (100 nM) had no significant effect on [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> and diameter of −/− BKβ<jats:sub>1</jats:sub>-pressurized (60 mmHg) arteries. These results are consistent with the idea that Ca<jats:sup>2+</jats:sup> sparks in arterial smooth muscle cells limit myogenic tone through activation of BK channels. The activation of BK channels by Ca<jats:sup>2+</jats:sup> sparks reduces the voltage-dependent Ca<jats:sup>2+</jats:sup> influx and [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> through tonic hyperpolarization. Deletion of BKβ<jats:sub>1</jats:sub> disrupts this negative feedback mechanism, leading to increased arterial tone through an increase in global [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>. </jats:p>","journal":"Journal of Applied Physiology","year":2001,"id":675136,"datarank":0.6064576901751826,"base_score":4.04305126783455,"endowment":4.04305126783455,"self_citation_contribution":0.6064576901751826,"citation_network_contribution":0.0,"self_endowment_contribution":0.6064576901751826,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":56,"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":1764017,"name":"Birgit Lauterbach","orcid":null,"position":1,"is_corresponding":false},{"id":84862,"name":"Hermann Haller","orcid":null,"position":2,"is_corresponding":false},{"id":1390379,"name":"Olaf Pongs","orcid":null,"position":3,"is_corresponding":false},{"id":334082,"name":"Friedrich C. Luft","orcid":"0000-0002-8635-1199","position":4,"is_corresponding":false},{"id":961210,"name":"Maik Gollasch","orcid":"0000-0003-2797-1934","position":5,"is_corresponding":false},{"id":1764016,"name":"Matthias Löhn","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"β<sub>1</sub>-subunit of BK channels regulates arterial wall [Ca<sup>2+</sup>] and diameter in mouse cerebral arteries","abstract":"<jats:p> Mice with a disrupted β<jats:sub>1</jats:sub>(BKβ<jats:sub>1</jats:sub>)-subunit of the large-conductance Ca<jats:sup>2+</jats:sup>-activated K<jats:sup>+</jats:sup> (BK) channel gene develop systemic hypertension and cardiac hypertrophy, which is likely caused by uncoupling of Ca<jats:sup>2+</jats:sup> sparks to BK channels in arterial smooth muscle cells. However, little is known about the physiological levels of global intracellular Ca<jats:sup>2+</jats:sup> concentration ([Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>) and its regulation by Ca<jats:sup>2+</jats:sup> sparks and BK channel subunits. We utilized a BKβ<jats:sub>1</jats:sub> knockout C57BL/6 mouse model and studied the effects of inhibitors of ryanodine receptor and BK channels on the global [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> and diameter of small cerebral arteries pressurized to 60 mmHg. Ryanodine (10 μM) or iberiotoxin (100 nM) increased [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> by ∼75 nM and constricted +/+ BKβ<jats:sub>1</jats:sub> wild-type arteries (pressurized to 60 mmHg) with myogenic tone by ∼10 μm. In contrast, ryanodine (10 μM) or iberiotoxin (100 nM) had no significant effect on [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> and diameter of −/− BKβ<jats:sub>1</jats:sub>-pressurized (60 mmHg) arteries. These results are consistent with the idea that Ca<jats:sup>2+</jats:sup> sparks in arterial smooth muscle cells limit myogenic tone through activation of BK channels. The activation of BK channels by Ca<jats:sup>2+</jats:sup> sparks reduces the voltage-dependent Ca<jats:sup>2+</jats:sup> influx and [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> through tonic hyperpolarization. Deletion of BKβ<jats:sub>1</jats:sub> disrupts this negative feedback mechanism, leading to increased arterial tone through an increase in global [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>. </jats:p>","is_dataset_classified":null,"base_score":4.04305126783455,"endowment":4.04305126783455,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11509535","pmcid":null,"openalex_id":"https://openalex.org/W2264880549","authors":[],"funders":[],"total_grants":0,"fwci":1.2307,"citation_percentile":0.78886566,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":3},{"year":2014,"count":4},{"year":2015,"count":4},{"year":2018,"count":2},{"year":2019,"count":1},{"year":2020,"count":3},{"year":2021,"count":7},{"year":2022,"count":1},{"year":2023,"count":2},{"year":2024,"count":1},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.physiology.org/doi/pdf/10.1152/jappl.2001.91.3.1350","host_type":"publisher"},{"url":"https://doi.org/10.1152/jappl.2001.91.3.1350","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11509535","host_type":"repository"}],"fields_of_study":["Ion channel regulation and function","Cardiac electrophysiology and arrhythmias","Neuroscience and Neuropharmacology Research","Animals","Calcium","Cardiomegaly","Cerebral Arteries","Cerebrovascular Circulation","Hypertension","Large-Conductance Calcium-Activated Potassium Channels","Mice","Mice, Inbred C57BL","Mice, Knockout","Peptides","Potassium Channels","Potassium Channels, Calcium-Activated","Ryanodine","Vasoconstriction"],"mesh_terms":["Animals","Calcium","Cerebral Arteries","Cerebrovascular Circulation","Cardiomegaly","Hypertension","Mice, Inbred C57BL","Peptides","Ryanodine","Vasoconstriction","Potassium Channels","Mice, Knockout","Potassium Channels, Calcium-Activated","Large-Conductance Calcium-Activated Potassium Channels","Mice"],"keywords":["Iberiotoxin","BK channel","Ryanodine receptor","Chemistry","Hyperpolarization (physics)","Internal medicine","Vascular smooth muscle","Cerebral arteries","Endocrinology","Biophysics","Anatomy","Potassium channel","Intracellular","Biology","Medicine","Smooth muscle","Biochemistry","Stereochemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T19:56:00.312848Z","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":[]}