Affinage

KCNMA1

Calcium-activated potassium channel subunit alpha-1 · UniProt Q12791

Length
1236 aa
Mass
137.6 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNMA1 encodes the pore-forming α subunit of the large-conductance calcium- and voltage-activated potassium (BK) channel, a ubiquitous regulator of membrane excitability, epithelial ion secretion, and mitochondrial oxidative stress responses. The channel is activated by membrane depolarization and intracellular Ca²⁺ supplied through nanodomain coupling with voltage-gated (Cav3) and TRP-family (TRPV1, TRPV4/TRPC1) calcium channels (PMID:23626738, PMID:24147119, PMID:25511389); its biophysical properties are extensively tuned by alternative splicing—notably the STREX exon, which inverts PKA regulation and is itself controlled by steroid hormones and pregnancy (PMID:12016222, PMID:12032350, PMID:16102753)—by CaMKII phosphorylation of Thr107 that switches ethanol sensitivity (PMID:16341213), by auxiliary β subunits that modulate Ca²⁺ sensitivity, kinetics, and surface trafficking (PMID:21178105, PMID:27165430), and by Nrf2-dependent transcription through ARE elements in the promoter (PMID:32147517). A C-terminal splice insert targets the channel to the mitochondrial inner membrane where it limits reactive oxygen species production and mediates ischemic preconditioning cardioprotection (PMID:23754429, PMID:25072914). Gain-of-function mutations (D434G, N999S) that shift activation to hyperpolarized potentials cause paroxysmal dyskinesia and epilepsy, while loss-of-function mutations that abolish or reduce BK current cause neurodevelopmental channelopathy (PMID:31152168, PMID:35819138).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1991 High

    Cloning of Drosophila slowpoke established a new gene family encoding Ca²⁺-activated K⁺ channels structurally related to voltage-gated K⁺ channels, resolving the molecular identity of BK channels.

    Evidence Genomic/cDNA cloning and genetic loss-of-function in Drosophila muscles and neurons

    PMID:1857984

    Open questions at the time
    • Mammalian ortholog not yet cloned
    • Mechanism of Ca²⁺ sensing unknown
    • Subunit stoichiometry undetermined
  2. 1997 High

    Discovery that a cysteine-rich C-terminal splice insert shifts voltage dependence by −20 to −30 mV established alternative splicing as a direct mechanism for tuning BK channel gating.

    Evidence Expression of defined splice constructs in Xenopus oocytes with electrophysiology

    PMID:9115223

    Open questions at the time
    • Number and functional impact of other splice sites unknown
    • In vivo relevance of this particular insert not tested
  3. 1998 High

    Co-expression of KCNMA1 with Slack demonstrated that BK α subunits can form heteromeric channels with distinct conductance and pharmacology, expanding the functional repertoire beyond homomeric assemblies.

    Evidence Heterologous co-expression with single-channel patch-clamp

    PMID:10196543

    Open questions at the time
    • Stoichiometry and structure of heteromeric complex unknown
    • In vivo prevalence of Slo/Slack heteromers not established
  4. 2002 High

    The STREX exon was shown to be required for opposing regulation by cAMP/cGMP kinases and to increase oxidation and Ca²⁺ sensitivity, while steroid hormones (glucocorticoids vs. androgens) regulate STREX inclusion, establishing hormone-controlled alternative splicing as a major regulatory axis of BK channel function.

    Evidence Splice variant electrophysiology, pharmacological modulation, RT-PCR with receptor antagonist blockade in chromaffin cells

    PMID:12016222 PMID:12032350

    Open questions at the time
    • Splicing trans-factors mediating steroid effects not identified
    • Structural basis of STREX-dependent PKA regulation unknown
  5. 2004 High

    Bidirectional genetic manipulation of slo in Drosophila proved that BK channel expression is both induced by ethanol and necessary/sufficient for rapid alcohol tolerance, while Aplysia studies showed developmental splicing switches PKA regulation—together establishing BK channels as key mediators of neural adaptation.

    Evidence Drosophila LOF/GOF behavioral assays; Aplysia splice isoform electrophysiology with PKA application

    PMID:15375169 PMID:15569939

    Open questions at the time
    • Mammalian in vivo ethanol tolerance role not directly tested
    • Signal controlling developmental splice switching unknown
  6. 2005 High

    Identification of CaMKII phosphorylation at Thr107 as a molecular switch that progressively increases BK activity and converts ethanol responses from activation to inhibition resolved how post-translational modification tunes pharmacological sensitivity at a single residue.

    Evidence Site-directed mutagenesis, in vitro CaMKII phosphorylation, patch-clamp electrophysiology

    PMID:16341213

    Open questions at the time
    • In vivo phosphorylation state at Thr107 under ethanol exposure not measured
    • Interplay with STREX-dependent PKA regulation unclear
  7. 2005 Medium

    Estrogen and progesterone were shown to oppositely regulate STREX inclusion, with pregnancy progressively eliminating ~80% of STREX transcripts, providing a mechanism for altered BK channel regulation during gestation.

    Evidence RT-PCR with estrogen receptor antagonist blockade and pregnancy time-course analysis

    PMID:16102753

    Open questions at the time
    • Single lab finding; independent replication not documented
    • Downstream functional consequence on uterine BK current not directly measured
  8. 2008 High

    Genetic knockout studies demonstrated that KCNMA1 is the primary K⁺ secretory channel in colonic and salivary duct epithelia, with aldosterone transcriptionally upregulating its expression, establishing the channel's essential role in epithelial ion transport.

    Evidence BK α-subunit KO mice, Ussing chamber flux measurements, iberiotoxin/paxilline pharmacology, actinomycin D transcription block

    PMID:18216162 PMID:18617563 PMID:22322970

    Open questions at the time
    • Aldosterone-responsive transcription factors binding KCNMA1 promoter not identified at this time
    • Contribution of specific β subunits to epithelial targeting incompletely defined
  9. 2012 High

    Single-molecule imaging in vascular smooth muscle revealed that BKα membrane dynamics are restricted by β1 subunit co-association, actin cytoskeleton, and direct caveolin-1 interaction, establishing a framework for how the channel is spatially organized in signaling microdomains.

    Evidence Single-molecule TIRF, FRAP, FRET, cytochalasin D perturbation in VSMCs

    PMID:22301058

    Open questions at the time
    • Structural basis of caveolin-1 interaction not resolved
    • Whether caveolar localization is required for functional coupling to Ca²⁺ sources unknown
  10. 2013 High

    Physical nanodomain coupling of KCNMA1 with Cav3 (via the S0 segment), TRPV1, and subsequently TRPV4/TRPC1 was demonstrated, showing that local Ca²⁺ microdomains from diverse sources activate BK channels within submilliseconds to control neuronal spike repolarization and vascular tone.

    Evidence Reciprocal co-IP from brain tissue and cell lines, BAPTA vs. EGTA chelation kinetics, patch-clamp electrophysiology, vascular tension assays

    PMID:23626738 PMID:24147119 PMID:25511389

    Open questions at the time
    • Atomic-resolution structure of BK–Cav3 or BK–TRPV1 complex unavailable
    • Relative in vivo prevalence of different Ca²⁺ source complexes across tissues unknown
  11. 2013 High

    A 50-amino acid C-terminal splice insert was identified as necessary and sufficient for mitochondrial targeting of BK channels; KCNMA1 KO mice lacked mitoBK current and cardioprotection, definitively assigning the mitochondrial BK channel to the KCNMA1 gene.

    Evidence Mitochondrial fractionation, electron microscopy, mitoplast patch-clamp, KCNMA1 KO mice, ischemia-reperfusion and ROS assays

    PMID:23754429 PMID:25072914

    Open questions at the time
    • Mechanism of mitoBK import into inner membrane not resolved
    • Physiological Ca²⁺ source activating mitoBK in the matrix unknown
  12. 2019 High

    Systematic electrophysiological characterization of KCNMA1 disease mutations established that gain-of-function alleles (D434G, N999S) shift activation negatively causing dyskinesia/epilepsy while loss-of-function alleles abolish current causing neurodevelopmental syndromes, defining KCNMA1-linked channelopathy as a bidirectional spectrum.

    Evidence Patch-clamp of mutant channels in HEK cells, exome sequencing of patients, knock-in mouse models with seizure threshold and dyskinesia assays

    PMID:31152168 PMID:35819138

    Open questions at the time
    • Cell-type-specific consequences of mutations in native neurons not fully characterized
    • No genotype-targeted therapy validated
  13. 2020 High

    Nrf2 was identified as a direct transcriptional activator of KCNMA1 via ARE elements in the promoter, linking antioxidant signaling to BK channel expression in coronary arteries and providing a transcriptional mechanism for oxidative-stress-dependent channel regulation.

    Evidence Nrf2 KO mice, promoter-luciferase reporter, adenoviral rescue, patch-clamp in coronary smooth muscle

    PMID:32147517

    Open questions at the time
    • Whether Nrf2 regulation generalizes beyond vascular smooth muscle not tested
    • Other transcription factors acting on KCNMA1 promoter not comprehensively mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of BK channel coupling to its diverse Ca²⁺ source partners, the mechanisms governing splice-insert-directed mitochondrial import, comprehensive mapping of transcription factor inputs to the KCNMA1 promoter across tissues, and development of mutation-specific therapeutic strategies for KCNMA1 channelopathies.
  • No high-resolution structure of BK in complex with any Ca²⁺ channel partner
  • Mitochondrial import pathway for mitoBK splice variant unknown
  • No genotype-targeted pharmacotherapy validated for KCNMA1 channelopathy

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 7 GO:0140299 molecular sensor activity 3
Localization
GO:0005886 plasma membrane 8 GO:0005739 mitochondrion 2
Pathway
R-HSA-112316 Neuronal System 6 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2
Partners
CACNA1GCAV1KCNMB1KCNMB4KCNT1TRPC1TRPV1TRPV4
Complex memberships
BK channel (α4 homotetramer or α4β4 complex)Cav3–BK nanodomain complexTRPV1–BK nanodomain complexTRPV4–TRPC1–BK complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 The Drosophila slowpoke (slo) locus encodes a structural component of Ca2+-activated K+ channels; the predicted polypeptide shares similarity with voltage-activated K+ channel polypeptides in domains essential for function, establishing slo as the founding member of the BK channel gene family. Genomic and cDNA cloning, sequencing, genetic loss-of-function (slo mutations abolish Ca2+-activated K+ current in muscles and neurons) Science High 1857984
1998 KCNMA1 (Slo) and Slack co-express to form intermediate-conductance (60–180 pS) calcium-activated K+ channels with distinct pharmacological properties not matching either subunit alone, identifying a heteromeric channel assembly mechanism. Co-expression in heterologous cells, single-channel patch-clamp electrophysiology Nature Neuroscience High 10196543
1997 A cysteine-rich 59-amino acid alternative splice insert in the C-terminal region of the Slo (KCNMA1) subunit shifts the conductance-voltage curve by −20 to −30 mV when expressed in Xenopus oocytes, demonstrating that alternative splicing directly modulates BK channel voltage dependence. cDNA cloning, expression in Xenopus oocytes, electrophysiology Journal of Biological Chemistry High 9115223
2005 CaMKII phosphorylates Thr107 in the cytosolic S0-S1 loop of BK channel α-subunit (Slo/KCNMA1), progressively increasing channel activity and switching ethanol responses from activation to inhibition, acting as a 'molecular dimmer switch' for alcohol modulation. Site-directed mutagenesis of Thr107, in vitro CaMKII phosphorylation assay, patch-clamp electrophysiology Nature Neuroscience High 16341213
2002 The STREX alternative exon of KCNMA1 (Slo) is required for opposing regulation by cAMP- and cGMP-dependent protein kinases; inclusion of the cysteine-rich STREX exon also increases channel sensitivity to inhibition by oxidation 10-fold and increases calcium sensitivity, while these effects depend on co-assembly with β1 subunits and N-terminal variation. Splice variant expression in cells, electrophysiology, pharmacological modulation, oxidation assays Journal of Biological Chemistry High 12016222
2002 Glucocorticoids decrease and adrenal androgens (DHEA, androstenedione, testosterone) increase inclusion of the STREX exon in Slo (KCNMA1) transcripts in bovine chromaffin cells, with glucocorticoid effects blocked by the glucocorticoid receptor antagonist RU38486, demonstrating steroid hormone-regulated alternative splicing of KCNMA1. Cell culture treatment, RT-PCR quantification of splice variants, pharmacological receptor blockade PNAS High 12032350
2013 MitoBKCa (mitochondrial BK channel) is encoded by KCNMA1 and a 50-amino acid C-terminal splice insert is essential for its mitochondrial targeting; KCNMA1 knockout mice lack NS1619-mediated cardioprotection, confirming mitoBK functional identity. Biochemical fractionation of purified mitochondria, Western blotting, electron microscopy, KCNMA1 KO mouse model, pharmacological cardioprotection assay PNAS High 23754429
2013 Cav3 (T-type) calcium channels physically associate with KCa1.1 (KCNMA1) at the transmembrane S0 segment of the KCa1.1 N-terminus, enabling low-voltage activation of KCa1.1 current with a 50 mV negative shift in voltage for activation; this Cav3-KCa1.1 complex functions in medial vestibular neurons to contribute to spike repolarization. Co-immunoprecipitation from tsA-201 cells and rat brain, heterologous co-expression, patch-clamp electrophysiology, pharmacological blockade PLoS ONE High 23626738
2013 TRPV1 and BK (KCNMA1) channels form a functional complex in dorsal root ganglion neurons; Ca2+ influx through TRPV1 activates BK channels within submilliseconds, with local Ca2+ concentration estimated >10 µM, and the interaction is blocked by fast Ca2+ chelator BAPTA but not slow chelator EGTA; the complex was confirmed by co-immunoprecipitation. Patch-clamp electrophysiology with infrared laser activation, BAPTA/EGTA chelation, fluorescence co-localization, co-immunoprecipitation PLoS ONE High 24147119
2014 EETs (11,12-EET) induce smooth muscle hyperpolarization and vascular relaxation in human internal mammary arteries by targeting a TRPV4-TRPC1-KCa1.1 (KCNMA1) complex; TRPC1 acts as the linker between TRPV4 and KCa1.1α, as demonstrated by physical interaction and functional reconstitution. Co-immunoprecipitation, HEK293 overexpression reconstitution, microelectrode membrane potential recording, vascular tension assay Biochimica et Biophysica Acta High 25511389
2012 The pore-forming α subunit of KCa1.1 (KCNMA1) co-immunoprecipitates with β1 integrins in rheumatoid arthritis fibroblast-like synoviocytes; blocking KCa1.1 disrupts calcium homeostasis and leads to sustained Akt phosphorylation and talin recruitment to β1 integrins, regulating cell adhesion. Co-immunoprecipitation, patch-clamp electrophysiology, siRNA knockdown, calcium imaging, Western blotting FASEB Journal Medium 28428266
2011 KCa1.1 (KCNMA1) is the major K+ channel at the plasma membrane of rheumatoid arthritis fibroblast-like synoviocytes; blocking KCa1.1 perturbs calcium homeostasis and inhibits proliferation, VEGF/IL-8/pro-MMP-2 production, and migration/invasion of RA-FLS. Patch-clamp electrophysiology, siRNA knockdown, pharmacological blockade with iberiotoxin/paxilline, functional invasion/migration assays Journal of Biological Chemistry High 22074915
2012 TMPRSS3 loss-of-function mutation impairs Kcnma1 channel membrane expression at the neck of cochlear inner hair cells, linking TMPRSS3 serine protease activity to proper Kcnma1 surface localization and outward K+ current maturation. Patch-clamp electrophysiology, proteomic analysis, immunohistochemistry in wild-type vs. Tmprss3 mutant mice Human Molecular Genetics Medium 23255163
2005 Estrogen decreases STREX exon inclusion in Slo (KCNMA1) transcripts, an effect blocked by estrogen receptor antagonist ICI 182,780; progesterone opposes estrogen's effect; pregnancy progressively reduces STREX transcripts ~80% at term, providing a mechanism for altered PKA regulation of Slo during pregnancy. RT-PCR quantification of splice variants, estrogen receptor antagonist blockade, pregnancy time-course analysis FEBS Letters Medium 16102753
2003 The slo core-linker region (not the tail domain) is the critical determinant of differential BK channel responses to ethanol; channels with mslo-type core-linker are consistently activated by ethanol while channels with bslo-type core-linker show inhibition, refractoriness, or activation. Chimeric channel construction (core-tail domain swaps between mslo and bslo), single-channel patch-clamp in cell-free membrane patches Alcoholism: Clinical and Experimental Research High 14574235
2008 Aldosterone stimulates colonic K+ secretion exclusively via luminal KCa1.1 (KCNMA1) BK channels in mouse distal colon; high K+ diet increases BK α- and β2-subunit mRNA and promotes luminal membrane expression of BK channels; effect is absent in BK α-subunit knockout mice. Ussing chamber short-circuit current measurement, iberiotoxin pharmacological blockade, BK α-subunit KO mice, immunohistochemistry, semi-quantitative RT-PCR Journal of Physiology High 18617563
2012 Aldosterone induces active K+ secretion in rat distal colon by transcriptionally upregulating both Kcnma1 and Kcnn4c channel expression at the mucosal membrane; actinomycin D (RNA synthesis inhibitor) prevents the aldosterone-induced mRNA increase, demonstrating transcriptional regulation. Ussing chamber 86Rb flux measurements, iberiotoxin/TRAM-34 pharmacological dissection, Western blotting, quantitative RT-PCR, actinomycin D blockade American Journal of Physiology – Cell Physiology High 22322970
2008 KCa1.1 (KCNMA1) channels localize to the apical membranes of striated and excretory duct cells (but not granular duct cells) in the mouse submandibular gland; genetic null mutation of KCa1.1 abolishes K+ secretion and eliminates its flow-rate dependence, demonstrating KCa1.1 as the primary K+ secretory pathway in salivary gland ducts. KCa1.1 null mice, ionic flux measurement, paxilline pharmacological blockade, immunohistochemistry for subcellular localization American Journal of Physiology – Cell Physiology High 18216162
2012 In vascular smooth muscle cells (VSMCs), BKα (KCNMA1) subunit mobility on the plasma membrane is strongly restricted by co-association with β1 auxiliary subunit (~50% reduction in diffusion), cytoskeletal actin, and direct interaction with caveolin-1 (Cav1), as shown by FRET; disrupting actin with cytochalasin D increases BKα mobility. Single-molecule TIRF microscopy, FRAP, FRET analysis, cytochalasin D/jasplakinolide actin manipulation American Journal of Physiology – Cell Physiology High 22301058
2014 Electrophysiological recordings from KCNMA1 knockout cardiomyocyte mitoplasts confirm paxilline- and NS11021-sensitive BK currents of 190 pS conductance present in wild-type but absent in BK−/− cells; BK−/− hearts show increased post-anoxic ROS production and impaired ischemic preconditioning protection, demonstrating mitoBK regulates mitochondrial oxidative state and cardioprotection. Mitoplast patch-clamp electrophysiology, KCNMA1 KO mice, ex vivo ischemia-reperfusion model, ROS measurement, oxidative phosphorylation capacity PLoS ONE High 25072914
2020 Nrf2 directly transcriptionally regulates KCNMA1 expression by binding to antioxidant response elements (AREs) in the KCNMA1 promoter; Nrf2 KO mice show reduced BK-α mRNA and protein, decreased BK current density in coronary arterial smooth muscle cells, and adenoviral Nrf2 expression or pharmacological Nrf2 activation rescues BK channel expression and activity. Nrf2 KO mice, promoter-luciferase reporter assay, adenoviral Nrf2 overexpression, patch-clamp electrophysiology, RT-PCR, Western blotting Journal of Molecular and Cellular Cardiology High 32147517
2016 Loss of plasma membrane expression of KCa1.1 α-subunit (KCNMA1) occurs in myotonic dystrophy type 1 (DM1) myoblasts; inhibiting KCa1.1 in healthy myoblasts elevates cytosolic calcium and alters NFκB levels, increases proliferation, and impairs migration and myotube fusion—phenotypes matching DM1; re-introducing functional KCa1.1 α-subunits into DM1 myoblasts normalizes proliferation and rescues Mef2 expression. siRNA knockdown, pharmacological blockade, overexpression in DM1 myoblasts, calcium imaging, functional proliferation/migration/fusion assays, Western blotting Cell Death & Disease High 27763639
2004 In Drosophila, slo (KCNMA1 ortholog) K+ channel gene expression is induced by ethanol sedation in the nervous system and mediates rapid drug tolerance; a slo loss-of-function mutation prevents tolerance acquisition, while transgenic induction of slo in naive animals phenocopies tolerance. Drosophila genetic loss-of-function mutation, inducible transgene expression, behavioral ethanol tolerance assays PNAS High 15569939
2019 KCNMA1 gain-of-function mutations (D434G, N999S) shift BK channel activation to negative potentials with faster activation and slower deactivation, while loss-of-function mutations (e.g., Gly375Arg, Gly356Arg, Ser351Tyr) abolish or reduce BK current and shift activation curves toward positive potentials; these properties are established as the mechanistic basis of KCNMA1-linked channelopathy. Patch-clamp electrophysiology of mutant channels expressed in HEK cells, exome/genome sequencing Human Molecular Genetics High 31152168
2022 The KCNMA1-N999S mutation produces stronger BK channel gain-of-function than D434G, with greater negative shift in V1/2, faster activation, and slower deactivation; Kcnma1N999S/WT mice show increased BK currents, increased action potential firing, decreased seizure threshold, and paroxysmal dyskinesia; the double mutation N999S/R1128W shows no additional functional change over N999S alone; acetazolamide has no direct modulatory action on BK channels. Patch-clamp electrophysiology in HEK293T cells and transgenic mice, seizure threshold testing, in vivo behavioral paroxysmal dyskinesia assay, action potential voltage commands eLife High 35819138
2010 β4 subunit increases KCa1.1 (Slo/KCNMA1) responsiveness to Ca2+ at physiological hair cell operating voltages (around −50 mV); β4 and β1 together reduce surface expression of Slo in chick cochlear hair cells; β4-mediated Ca2+ sensitivity increase is associated with its role in electrical frequency tuning in low-frequency hair cells. Cloning of chick β4 and β1 subunits, heterologous expression, patch-clamp electrophysiology, surface expression quantification American Journal of Physiology – Cell Physiology Medium 21178105
2006 KCNMA1 gene amplification at chromosomal region 10q22 drives BK channel protein overexpression and increased BK currents in PC-3 prostate cancer cells; specific blockade of BK channels by iberiotoxin or KCNMA1 RNAi significantly inhibits K+ currents and cell proliferation. FISH for gene amplification, siRNA knockdown, iberiotoxin pharmacological blockade, whole-cell patch-clamp, proliferation assays Oncogene Medium 17146446
2016 The β3b regulatory subunit of KCa1.1 (KCNMA1) is expressed by highly invasive CD44high RA fibroblast-like synoviocytes; siRNA silencing of β3 (but not β1) reduces KCa1.1 channel density at the plasma membrane and inhibits RA-FLS invasiveness, identifying β3b-containing KCa1.1 as a disease-relevant channel complex. siRNA knockdown of β subunits, patch-clamp electrophysiology, flow cytometric sorting by CD44 expression, invasion assays Arthritis Research & Therapy Medium 27165430
2004 In Aplysia bag cell neurons, a PKA-regulated Slo-a splice isoform (containing a PKA consensus phosphorylation site) is expressed in adult but not juvenile neurons; PKA reduces open probability of Slo-a but not Slo-b; this developmental switch in splice isoform expression allows mature neurons to generate afterdischarges required for reproduction. cDNA library cloning, heterologous expression in CHO cells, patch-clamp electrophysiology, PKA catalytic subunit application, immunocytochemistry in adult vs. juvenile neurons Journal of Biological Chemistry High 15375169

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 A component of calcium-activated potassium channels encoded by the Drosophila slo locus. Science (New York, N.Y.) 550 1857984
2006 High-conductance potassium channels of the SLO family. Nature reviews. Neuroscience 446 17115074
2003 The sodium-activated potassium channel is encoded by a member of the Slo gene family. Neuron 219 12628167
2013 MitoBK(Ca) is encoded by the Kcnma1 gene, and a splicing sequence defines its mitochondrial location. Proceedings of the National Academy of Sciences of the United States of America 173 23754429
1998 Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits. Nature neuroscience 145 10196543
1997 A cysteine-rich domain defined by a novel exon in a slo variant in rat adrenal chromaffin cells and PC12 cells. The Journal of biological chemistry 123 9115223
1987 Nucleotide sequence of the streptolysin O (SLO) gene: structural homologies between SLO and other membrane-damaging, thiol-activated toxins. Infection and immunity 119 3502717
2019 KCNMA1-linked channelopathy. The Journal of general physiology 110 31427379
2006 KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer. Oncogene 109 17146446
2009 Role of KCNMA1 gene in breast cancer invasion and metastasis to brain. BMC cancer 106 19640305
2000 SLO-2, a K+ channel with an unusual Cl- dependence. Nature neuroscience 100 10903569
2007 The calcium-activated potassium channel, SLO-1, is required for the action of the novel cyclo-octadepsipeptide anthelmintic, emodepside, in Caenorhabditis elegans. International journal for parasitology 92 17583712
2012 Role of KCNMA1 in breast cancer. PloS one 82 22899999
2014 KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury. PloS one 80 25072914
2011 Genome wide association study identifies KCNMA1 contributing to human obesity. BMC medical genomics 74 21708048
2019 De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurological phenotypes. Human molecular genetics 71 31152168
1996 Reconstitution of transcytosis in SLO-permeabilized MDCK cells: existence of an NSF-dependent fusion mechanism with the apical surface of MDCK cells. The EMBO journal 65 8612570
2015 Over-expression of miR-31 or loss of KCNMA1 leads to increased cisplatin resistance in ovarian cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 64 26386726
2011 SLO-2 is cytoprotective and contributes to mitochondrial potassium transport. PloS one 58 22145034
2008 Aldosterone increases KCa1.1 (BK) channel-mediated colonic K+ secretion. The Journal of physiology 58 18617563
2005 CaM kinase II phosphorylation of slo Thr107 regulates activity and ethanol responses of BK channels. Nature neuroscience 57 16341213
2002 Interacting effects of N-terminal variation and strex exon splicing on slo potassium channel regulation by calcium, phosphorylation, and oxidation. The Journal of biological chemistry 56 12016222
2016 Homozygous KCNMA1 mutation as a cause of cerebellar atrophy, developmental delay and seizures. Human genetics 55 27567911
2021 An emerging spectrum of variants and clinical features in KCNMA1-linked channelopathy. Channels (Austin, Tex.) 52 34224328
2004 slo K(+) channel gene regulation mediates rapid drug tolerance. Proceedings of the National Academy of Sciences of the United States of America 52 15569939
2002 Opposing actions of adrenal androgens and glucocorticoids on alternative splicing of Slo potassium channels in bovine chromaffin cells. Proceedings of the National Academy of Sciences of the United States of America 52 12032350
2013 Low voltage activation of KCa1.1 current by Cav3-KCa1.1 complexes. PloS one 51 23626738
2016 KCa1.1, a calcium-activated potassium channel subunit alpha 1, is targeted by miR-17-5p and modulates cell migration in malignant pleural mesothelioma. Molecular cancer 46 27245839
2005 Alternative splicing of Slo channel gene programmed by estrogen, progesterone and pregnancy. FEBS letters 46 16102753
2013 Reduction of streptolysin O (SLO) pore-forming activity enhances inflammasome activation. Toxins 45 23744055
2011 SLO-1-channels of parasitic nematodes reconstitute locomotor behaviour and emodepside sensitivity in Caenorhabditis elegans slo-1 loss of function mutants. PLoS pathogens 44 21490955
2008 Apical maxi-K (KCa1.1) channels mediate K+ secretion by the mouse submandibular exocrine gland. American journal of physiology. Cell physiology 44 18216162
2014 Characterization of the Ca2+-gated and voltage-dependent K+-channel Slo-1 of nematodes and its interaction with emodepside. PLoS neglected tropical diseases 43 25521608
2011 KCa1.1 potassium channels regulate key proinflammatory and invasive properties of fibroblast-like synoviocytes in rheumatoid arthritis. The Journal of biological chemistry 43 22074915
2014 Epoxyeicosatrienoic acids act through TRPV4-TRPC1-KCa1.1 complex to induce smooth muscle membrane hyperpolarization and relaxation in human internal mammary arteries. Biochimica et biophysica acta 39 25511389
2008 Genetic variation in the KCNMA1 potassium channel alpha subunit as risk factor for severe essential hypertension and myocardial infarction. Journal of hypertension 39 18854754
2006 The SLO-1 BK channel of Caenorhabditis elegans is critical for muscle function and is involved in dystrophin-dependent muscle dystrophy. Journal of molecular biology 38 16527307
2011 KCa1.1 channel contributes to cell excitability in unmyelinated but not myelinated rat vagal afferents. American journal of physiology. Cell physiology 37 21325638
2017 KCNMA1 cooperating with PTK2 is a novel tumor suppressor in gastric cancer and is associated with disease outcome. Molecular cancer 36 28231797
2017 The Slo(w) path to identifying the mitochondrial channels responsible for ischemic protection. The Biochemical journal 36 28600454
2012 Molecular assembly and dynamics of fluorescent protein-tagged single KCa1.1 channel in expression system and vascular smooth muscle cells. American journal of physiology. Cell physiology 36 22301058
2014 SLO-2 potassium channel is an important regulator of neurotransmitter release in Caenorhabditis elegans. Nature communications 35 25300429
2011 Selective toxicity of the anthelmintic emodepside revealed by heterologous expression of human KCNMA1 in Caenorhabditis elegans. Molecular pharmacology 35 21415309
2011 Intragenic alternative splicing coordination is essential for Caenorhabditis elegans slo-1 gene function. Proceedings of the National Academy of Sciences of the United States of America 35 22084100
2018 Expanding the Phenotype of Homozygous KCNMA1 Mutations; Dyskinesia, Epilepsy, Intellectual Disability, Cerebellar and Corticospinal Tract Atrophy. Balkan medical journal 34 29545233
2002 Simvastatin treatment in the SLO syndrome: a safe approach? American journal of medical genetics 33 12407710
2013 TRPV1 channels are functionally coupled with BK(mSlo1) channels in rat dorsal root ganglion (DRG) neurons. PloS one 32 24147119
2021 Integrating adaptive optics-SLO and OCT for multimodal visualization of the human retinal pigment epithelial mosaic. Biomedical optics express 31 33796365
2013 Transplantation KCNMA1 modified bone marrow-mesenchymal stem cell therapy for diabetes mellitus-induced erectile dysfunction. Andrologia 30 23646921
2006 Regulation of alternative splicing of Slo K+ channels in adrenal and pituitary during the stress-hyporesponsive period of rat development. Endocrinology 30 16675526
2022 BK channel properties correlate with neurobehavioral severity in three KCNMA1-linked channelopathy mouse models. eLife 29 35819138
2020 A Gain-of-Function Mutation in KCNMA1 Causes Dystonia Spells Controlled With Stimulant Therapy. Movement disorders : official journal of the Movement Disorder Society 26 32633875
2019 Group A Streptococcus Induces LAPosomes via SLO/β1 Integrin/NOX2/ROS Pathway in Endothelial Cells That Are Ineffective in Bacterial Killing and Suppress Xenophagy. mBio 26 31575768
2015 The Cyclooctadepsipeptide Anthelmintic Emodepside Differentially Modulates Nematode, Insect and Human Calcium-Activated Potassium (SLO) Channel Alpha Subunits. PLoS neglected tropical diseases 26 26437177
2019 Comparative gain-of-function effects of the KCNMA1-N999S mutation on human BK channel properties. Journal of neurophysiology 25 31851553
2015 KCa1.1 inhibition attenuates fibroblast-like synoviocyte invasiveness and ameliorates disease in rat models of rheumatoid arthritis. Arthritis & rheumatology (Hoboken, N.J.) 25 25252152
2012 Aldosterone induces active K⁺ secretion by enhancing mucosal expression of Kcnn4c and Kcnma1 channels in rat distal colon. American journal of physiology. Cell physiology 25 22322970
2017 Behavioral Deficits Following Withdrawal from Chronic Ethanol Are Influenced by SLO Channel Function in Caenorhabditis elegans. Genetics 24 28546434
2012 Worms take to the slo lane: a perspective on the mode of action of emodepside. Invertebrate neuroscience : IN 24 22539031
2012 Tmprss3 loss of function impairs cochlear inner hair cell Kcnma1 channel membrane expression. Human molecular genetics 24 23255163
2018 Targeting KCa1.1 Channels with a Scorpion Venom Peptide for the Therapy of Rat Models of Rheumatoid Arthritis. The Journal of pharmacology and experimental therapeutics 23 29453198
2007 SLO, SLO, quick, quick, slow: calcium-activated potassium channels as regulators of Caenorhabditis elegans behaviour and targets for anthelmintics. Invertebrate neuroscience : IN 23 17962986
2019 KCNMA1 Expression is Downregulated in Colorectal Cancer via Epigenetic Mechanisms. Cancers 22 30791468
2008 Deficit of Kcnma1 mRNA expression in the dentate gyrus of epileptic rats. Neuroreport 22 18695509
2004 Regulation of Slo potassium channel alternative splicing in the pituitary by gonadal testosterone. Journal of neuroendocrinology 22 15049854
2010 β4-subunit increases Slo responsiveness to physiological Ca2+ concentrations and together with β1 reduces surface expression of Slo in hair cells. American journal of physiology. Cell physiology 21 21178105
2006 Diabetes-induced changes in the alternative splicing of the slo gene in corporal tissue. European urology 21 17150299
2017 Mus musculus-microRNA-449a ameliorates neuropathic pain by decreasing the level of KCNMA1 and TRPA1, and increasing the level of TPTE. Molecular medicine reports 20 28498403
2003 Distinct regions of the slo subunit determine differential BKCa channel responses to ethanol. Alcoholism, clinical and experimental research 20 14574235
2020 Gene-gene and gene-lifestyle interactions of AKAP11, KCNMA1, PUM1, SPTBN1, and EPDR1 on osteoporosis risk in middle-aged adults. Nutrition (Burbank, Los Angeles County, Calif.) 19 32619791
2017 KCa1.1 channels regulate β1-integrin function and cell adhesion in rheumatoid arthritis fibroblast-like synoviocytes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 19 28428266
2016 SLO BK Potassium Channels Couple Gap Junctions to Inhibition of Calcium Signaling in Olfactory Neuron Diversification. PLoS genetics 19 26771544
2016 Functional KCa1.1 channels are crucial for regulating the proliferation, migration and differentiation of human primary skeletal myoblasts. Cell death & disease 19 27763639
2015 Effect of scanning beam size on the lateral resolution of mouse retinal imaging with SLO. Optics letters 19 26670523
2005 Adenylate cyclase 5 and KCa1.1 channel are required for EGFR up-regulation of PCNA in native contractile rat basilar artery smooth muscle. The Journal of physiology 19 16284070
2002 Autonomous expression of the slo gene of the bicistronic nga-slo operon of Streptococcus pyogenes. Infection and immunity 19 11953421
2016 Different expression of β subunits of the KCa1.1 channel by invasive and non-invasive human fibroblast-like synoviocytes. Arthritis research & therapy 18 27165430
1998 Exoenzyme S from P. aeruginosa ADP ribosylates rab4 and inhibits transferrin recycling in SLO-permeabilized reticulocytes. Biochemical and biophysical research communications 18 9514923
2020 Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects. Frontiers in immunology 17 33363530
2019 KCa1.1 and Kv1.3 channels regulate the interactions between fibroblast-like synoviocytes and T lymphocytes during rheumatoid arthritis. Arthritis research & therapy 17 30612588
2018 Downregulation of the long noncoding RNA MBNL1-AS1 protects sevoflurane-pretreated mice against ischemia-reperfusion injury by targeting KCNMA1. Experimental & molecular medicine 17 30185781
2015 Enhancement of tumor initiation and expression of KCNMA1, MORF4L2 and ASPM genes in the adenocarcinoma of lung xenograft after vorinostat treatment. Oncotarget 17 25796627
2012 Role of the BK channel (KCa1.1) during activation of electrogenic K+ secretion in guinea pig distal colon. American journal of physiology. Gastrointestinal and liver physiology 17 23064759
2022 Molecular Mechanisms of Epileptic Encephalopathy Caused by KCNMA1 Loss-of-Function Mutations. Frontiers in pharmacology 16 35095492
2022 Identification and functional analysis of two new de novo KCNMA1 variants associated with Liang-Wang syndrome. Acta physiologica (Oxford, England) 16 35156297
2018 Visual Fixation Instability in Multiple Sclerosis Measured Using SLO-OCT. Investigative ophthalmology & visual science 16 29340646
2015 KCa1.1 is potential marker for distinguishing Ah-type baroreceptor neurons in NTS and contributes to sex-specific presynaptic neurotransmission in baroreflex afferent pathway. Neuroscience letters 16 26219983
2009 Inhibition of vascular calcium-gated chloride currents by blockers of KCa1.1, but not by modulators of KCa2.1 or KCa2.3 channels. British journal of pharmacology 16 19645713
2003 Subordination stress alters alternative splicing of the Slo gene in tree shrew adrenals. Hormones and behavior 16 12614648
2002 Pictogram naming in dyslexic and normal children assessed by SLO. Vision research 16 11888544
2020 Regulation of KCNMA1 transcription by Nrf2 in coronary arterial smooth muscle cells. Journal of molecular and cellular cardiology 15 32147517
2017 Survival and growth of C57BL/6J mice lacking the BK channel, Kcnma1: lower adult body weight occurs together with higher body fat. Physiological reports 15 28242822
2013 Enhanced K(+) secretion in dextran sulfate-induced colitis reflects upregulation of large conductance apical K(+) channels (BK; Kcnma1). American journal of physiology. Cell physiology 15 23986198
2011 The secretory KCa1.1 channel localises to crypts of distal mouse colon: functional and molecular evidence. Pflugers Archiv : European journal of physiology 15 21822598
2016 A DNA element in the slo gene modulates ethanol tolerance. Alcohol (Fayetteville, N.Y.) 14 26992698
2016 BK Knockout by TALEN-Mediated Gene Targeting in Osteoblasts: KCNMA1 Determines the Proliferation and Differentiation of Osteoblasts. Molecules and cells 14 27329042
2015 Active Site Dynamical Effects in the Hydrogen Transfer Rate-limiting Step in the Catalysis of Linoleic Acid by Soybean Lipoxygenase-1 (SLO-1): Primary and Secondary Isotope Contributions. The journal of physical chemistry. B 14 26079999
2004 The appearance of a protein kinase A-regulated splice isoform of slo is associated with the maturation of neurons that control reproductive behavior. The Journal of biological chemistry 14 15375169
2021 Lisdexamfetamine Therapy in Paroxysmal Non-kinesigenic Dyskinesia Associated with the KCNMA1-N999S Variant. Movement disorders clinical practice 13 35141357
2019 Effects of Single Nucleotide Polymorphisms in Human KCNMA1 on BK Current Properties. Frontiers in molecular neuroscience 13 31849601