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  1. Article: TRPC1 channel clustering during store-operated Ca

    Manning, Declan / Barrett-Jolley, Richard / Evans, Richard L / Dart, Caroline

    Frontiers in physiology

    2023  Volume 14, Page(s) 1141006

    Abstract: Skin is the largest organ in the human body with ∼95% of its surface made up of keratinocytes. These cells maintain a healthy skin barrier through regulated differentiation driven by ... ...

    Abstract Skin is the largest organ in the human body with ∼95% of its surface made up of keratinocytes. These cells maintain a healthy skin barrier through regulated differentiation driven by Ca
    Language English
    Publishing date 2023-03-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2023.1141006
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  2. Article: Store-operated calcium channels in skin.

    Manning, Declan / Dart, Caroline / Evans, Richard L

    Frontiers in physiology

    2022  Volume 13, Page(s) 1033528

    Abstract: The skin is a complex organ that acts as a protective layer against the external environment. It protects the internal tissues from harmful agents, dehydration, ultraviolet radiation and physical injury as well as conferring thermoregulatory control, ... ...

    Abstract The skin is a complex organ that acts as a protective layer against the external environment. It protects the internal tissues from harmful agents, dehydration, ultraviolet radiation and physical injury as well as conferring thermoregulatory control, sensation, immunological surveillance and various biochemical functions. The diverse cell types that make up the skin include 1) keratinocytes, which form the bulk of the protective outer layer; 2) melanocytes, which protect the body from ultraviolet radiation by secreting the pigment melanin; and 3) cells that form the secretory appendages: eccrine and apocrine sweat glands, and the sebaceous gland. Emerging evidence suggests that store-operated Ca
    Language English
    Publishing date 2022-10-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2022.1033528
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Verdict in the smooth muscle KATP channel case: guilty of blood pressure control but innocent of sudden death phenotype.

    Dart, Caroline

    Hypertension (Dallas, Tex. : 1979)

    2014  Volume 64, Issue 3, Page(s) 457–458

    MeSH term(s) Animals ; Blood Pressure/physiology ; KATP Channels/physiology ; Male ; Muscle, Smooth, Vascular/physiology
    Chemical Substances KATP Channels ; uK-ATP-1 potassium channel
    Language English
    Publishing date 2014-06-09
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.114.03289
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1488: Show issues Location:
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  4. Article ; Online: Selective block of K(ATP) channels: why the anti-diabetic sulphonylureas and rosiglitazone have more in common than we thought.

    Dart, Caroline

    British journal of pharmacology

    2012  Volume 167, Issue 1, Page(s) 23–25

    Abstract: Rosiglitazone, the thiazolidinedione class anti-diabetic withdrawn from Europe in 2010 amid reports of adverse cardiovascular effects, is revealed by Yu et al. in this issue of the British Journal of Pharmacology to be a selective blocker of ATP- ... ...

    Abstract Rosiglitazone, the thiazolidinedione class anti-diabetic withdrawn from Europe in 2010 amid reports of adverse cardiovascular effects, is revealed by Yu et al. in this issue of the British Journal of Pharmacology to be a selective blocker of ATP-sensitive potassium (K(ATP) ) channels. This seems little cause for excitement given that the closure of pancreatic K(ATP) channels is integral to insulin secretion; and sulphonylureas, which inhibit K(ATP) channels, are widely used to treat type II diabetes. However, rosiglitazone, whose primary targets are nuclear transcription factors that regulate genes involved in lipid metabolism, blocks K(ATP) channels by a novel mechanism different to that of the sulphonylureas and has a worrying preference for blood flow-regulating vascular K(ATP) channels. Identification of a new molecule that modulates K(ATP) channel gating will not only tell us more about how these complex metabolic sensors work but also raises questions as to whether rosiglitazone suppresses the cardiovascular system's ability to cope with metabolic stress - a claim that has dogged the sulphonylureas for many years.
    MeSH term(s) Humans ; KATP Channels/antagonists & inhibitors ; Potassium Channel Blockers/pharmacology ; Protein Subunits/antagonists & inhibitors ; Rosiglitazone ; Thiazolidinediones/pharmacology ; Vasodilator Agents/pharmacology
    Chemical Substances KATP Channels ; Potassium Channel Blockers ; Protein Subunits ; Thiazolidinediones ; Vasodilator Agents ; Rosiglitazone (05V02F2KDG)
    Language English
    Publishing date 2012-04-16
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/j.1476-5381.2012.01990.x
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  5. Article: Hypoxia and metabolic inhibitors alter the intracellular ATP:ADP ratio and membrane potential in human coronary artery smooth muscle cells.

    Yang, Mingming / Dart, Caroline / Kamishima, Tomoko / Quayle, John M

    PeerJ

    2020  Volume 8, Page(s) e10344

    Abstract: ATP-sensitive potassium ( ... ...

    Abstract ATP-sensitive potassium (K
    Language English
    Publishing date 2020-11-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2703241-3
    ISSN 2167-8359
    ISSN 2167-8359
    DOI 10.7717/peerj.10344
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  6. Article ; Online: Lipid microdomains and the regulation of ion channel function.

    Dart, Caroline

    The Journal of physiology

    2010  Volume 588, Issue Pt 17, Page(s) 3169–3178

    Abstract: Many types of ion channel localize to cholesterol and sphingolipid-enriched regions of the plasma membrane known as lipid microdomains or 'rafts'. The precise physiological role of these unique lipid microenvironments remains elusive due largely to ... ...

    Abstract Many types of ion channel localize to cholesterol and sphingolipid-enriched regions of the plasma membrane known as lipid microdomains or 'rafts'. The precise physiological role of these unique lipid microenvironments remains elusive due largely to difficulties associated with studying these potentially extremely small and dynamic domains. Nevertheless, increasing evidence suggests that membrane rafts regulate channel function in a number of different ways. Raft-enriched lipids such as cholesterol and sphingolipids exert effects on channel activity either through direct protein-lipid interactions or by influencing the physical properties of the bilayer. Rafts also appear to selectively recruit interacting signalling molecules to generate subcellular compartments that may be important for efficient and selective signal transduction. Direct interaction with raft-associated scaffold proteins such as caveolin can also influence channel function by altering gating kinetics or by affecting trafficking and surface expression. Selective association of ion channels with specific lipid microenvironments within the membrane is thus likely to be an important and fundamental regulatory aspect of channel physiology. This brief review highlights some of the existing evidence for raft modulation of channel function.
    MeSH term(s) Animals ; Humans ; Ion Channels/chemistry ; Ion Channels/physiology ; Lipids/chemistry ; Lipids/physiology ; Membrane Microdomains/chemistry ; Membrane Microdomains/physiology ; Signal Transduction/physiology
    Chemical Substances Ion Channels ; Lipids
    Language English
    Publishing date 2010-06-02
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/jphysiol.2010.191585
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  7. Article ; Online: Long QT syndrome-associated calmodulin variants disrupt the activity of the slowly activating delayed rectifier potassium channel.

    McCormick, Liam / Wadmore, Kirsty / Milburn, Amy / Gupta, Nitika / Morris, Rachael / Held, Marie / Prakash, Ohm / Carr, Joseph / Barrett-Jolley, Richard / Dart, Caroline / Helassa, Nordine

    The Journal of physiology

    2023  Volume 601, Issue 17, Page(s) 3739–3764

    Abstract: Calmodulin (CaM) is a highly conserved mediator of calcium ( ... ...

    Abstract Calmodulin (CaM) is a highly conserved mediator of calcium (Ca
    MeSH term(s) Humans ; Calmodulin/genetics ; Calmodulin/metabolism ; Calcium/metabolism ; HEK293 Cells ; Long QT Syndrome/genetics ; Mutation ; KCNQ1 Potassium Channel/genetics
    Chemical Substances Calmodulin ; potassium channel protein I(sk) ; Calcium (SY7Q814VUP) ; KCNQ1 Potassium Channel
    Language English
    Publishing date 2023-07-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP284994
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  8. Article ; Online: Soluble adenylyl cyclase links Ca

    Parker, Tony / Wang, Kai-Wen / Manning, Declan / Dart, Caroline

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 7317

    Abstract: ... ...

    Abstract Ca
    MeSH term(s) 1-Methyl-3-isobutylxanthine/pharmacology ; Adenylyl Cyclases/metabolism ; Calcium/metabolism ; Calcium Signaling/drug effects ; Cations, Divalent/metabolism ; Cell Line ; Colforsin/pharmacology ; Coronary Vessels/cytology ; Cyclic AMP/metabolism ; Cyclic AMP Response Element-Binding Protein/metabolism ; Estradiol/analogs & derivatives ; Estradiol/pharmacology ; Humans ; Muscle, Smooth, Vascular/cytology ; Muscle, Smooth, Vascular/metabolism ; Myocytes, Smooth Muscle/metabolism ; Phosphorylation/drug effects ; Thapsigargin/pharmacology ; Transcriptional Activation/drug effects
    Chemical Substances CREB1 protein, human ; Cations, Divalent ; Cyclic AMP Response Element-Binding Protein ; Colforsin (1F7A44V6OU) ; Estradiol (4TI98Z838E) ; Thapsigargin (67526-95-8) ; 2-hydroxyestradiol (AYU2L67YUU) ; Cyclic AMP (E0399OZS9N) ; ADCY10 protein, human (EC 4.6.1.1) ; Adenylyl Cyclases (EC 4.6.1.1) ; Calcium (SY7Q814VUP) ; 1-Methyl-3-isobutylxanthine (TBT296U68M)
    Language English
    Publishing date 2019-05-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-43821-3
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  9. Article ; Online: Neuronal and Cardiovascular Potassium Channels as Therapeutic Drug Targets: Promise and Pitfalls.

    Humphries, Edward S A / Dart, Caroline

    Journal of biomolecular screening

    2015  Volume 20, Issue 9, Page(s) 1055–1073

    Abstract: Potassium (K(+)) channels, with their diversity, often tissue-defined distribution, and critical role in controlling cellular excitability, have long held promise of being important drug targets for the treatment of dysrhythmias in the heart and abnormal ...

    Abstract Potassium (K(+)) channels, with their diversity, often tissue-defined distribution, and critical role in controlling cellular excitability, have long held promise of being important drug targets for the treatment of dysrhythmias in the heart and abnormal neuronal activity within the brain. With the exception of drugs that target one particular class, ATP-sensitive K(+) (KATP) channels, very few selective K(+) channel activators or inhibitors are currently licensed for clinical use in cardiovascular and neurological disease. Here we review what a range of human genetic disorders have told us about the role of specific K(+) channel subunits, explore the potential of activators and inhibitors of specific channel populations as a therapeutic strategy, and discuss possible reasons for the difficulty in designing clinically relevant K(+) channel modulators.
    MeSH term(s) Animals ; Cardiovascular Agents/pharmacology ; Cardiovascular Agents/therapeutic use ; Cardiovascular Diseases/drug therapy ; Cardiovascular Diseases/metabolism ; Humans ; Myocardium/metabolism ; Nervous System Diseases/drug therapy ; Nervous System Diseases/metabolism ; Neurons/metabolism ; Potassium Channel Blockers/pharmacology ; Potassium Channel Blockers/therapeutic use ; Potassium Channels/physiology
    Chemical Substances Cardiovascular Agents ; Potassium Channel Blockers ; Potassium Channels
    Language English
    Publishing date 2015-08-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1433680-7
    ISSN 1552-454X ; 1087-0571
    ISSN (online) 1552-454X
    ISSN 1087-0571
    DOI 10.1177/1087057115601677
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  10. Article ; Online: Hypoxia and metabolic inhibitors alter the intracellular ATP:ADP ratio and membrane potential in human coronary artery smooth muscle cells

    Mingming Yang / Caroline Dart / Tomoko Kamishima / John M. Quayle

    PeerJ, Vol 8, p e

    2020  Volume 10344

    Abstract: ATP-sensitive potassium (KATP) channels couple cellular metabolism to excitability, making them ideal candidate sensors for hypoxic vasodilation. However, it is still unknown whether cellular nucleotide levels are affected sufficiently to activate ... ...

    Abstract ATP-sensitive potassium (KATP) channels couple cellular metabolism to excitability, making them ideal candidate sensors for hypoxic vasodilation. However, it is still unknown whether cellular nucleotide levels are affected sufficiently to activate vascular KATP channels during hypoxia. To address this fundamental issue, we measured changes in the intracellular ATP:ADP ratio using the biosensors Perceval/PercevalHR, and membrane potential using the fluorescent probe DiBAC4(3) in human coronary artery smooth muscle cells (HCASMCs). ATP:ADP ratio was significantly reduced by exposure to hypoxia. Application of metabolic inhibitors for oxidative phosphorylation also reduced ATP:ADP ratio. Hyperpolarization caused by inhibiting oxidative phosphorylation was blocked by either 10 µM glibenclamide or 60 mM K+. Hyperpolarization caused by hypoxia was abolished by 60 mM K+ but not by individual K+ channel inhibitors. Taken together, these results suggest hypoxia causes hyperpolarization in part by modulating K+ channels in SMCs.
    Keywords Metabolic inhibitor ; Hypoxia ; ATP ; Membrane potential ; Potassium channels ; Medicine ; R ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher PeerJ Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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