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Modulation of ATP-sensitive potassium channel activity by ATP-binding cassette transporters

a model for channel regulation

by Tong-Yi Yao

  • 249 Want to read
  • 12 Currently reading

Published by s.n.] in [New Haven, Conn .
Written in English

  • Medicine

  • Edition Notes

    Thesis (M.D.) - Yale University, 1998.

    Statementby Tong-Yi Yao
    The Physical Object
    Paginationviii, 60 leaves ;
    Number of Pages60
    ID Numbers
    Open LibraryOL26393061M

    ATP channels can be pharmacologically modulated by a family of structurally diverse agents of varied potency and selectivity, collectively known as potassium channel openers and blockers.   The ATP-binding-cassette (ABC) transporters are evolutionary and extremely well-conserved transmembrane proteins involved in the transmembrane transport of a huge variety of substrates including.

    GO ion channel activity GO voltage-gated potassium channel activity GO protein binding GO potassium ion transport GO protein homooligomerization GO transmembrane transport. Closure of ATP-sensitive K+ channels (KATP channels) is a key step in glucose-stimulated insulin secretion. The precise mechanism(s) by which glucose metabolism regulates KATP channel activity, however, remains controversial. It is widely believed that the principal determinants are the intracellular concentrations of the metabolic ligands, ATP and ADP, which have opposing actions on KATP.

    ATP-sensitive K + (K ATP) channels integrate cellular energy signals with membrane electrical activity. Heteromultimers of KCNJencoded inwardly rectifying potassium Kir channels and ABCC9-encoded ATP-binding cassette SUR2A proteins, sarcolemmal K ATP channels are vital in heart energy homeostasis. Since then, the relationship between macrophage cholesterol levels and their inflammatory status is increasingly being strengthened and the role of cellular cholesterol transporters [e.g., ATP‐binding cassette transporter A1 (ABCA1), ATP‐binding cassette transporter G1 (ABCG1)] and extracellular cholesterol acceptors (e.g., high density.

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Modulation of ATP-sensitive potassium channel activity by ATP-binding cassette transporters by Tong-Yi Yao Download PDF EPUB FB2


The aim of this study was to characterize the relationship between ATP-Binding Cassette (ABC)Author: Tong-Yi Yao. An ATP-sensitive potassium channel (or K ATP channel) is a type of potassium channel that is gated by intracellular nucleotides, ATP and -sensitive potassium channels are composed of K ir 6.x-type subunits and sulfonylurea receptor (SUR) subunits, along with additional components.

K ATP channels are found in the plasma membrane; however some may also be found on subcellular HGNC:   The activity of ATP-sensitive potassium (K(ATP)) channels is governed by the concentration of intracellular ATP and ADP and is thus responsive to the metabolic status of the cell.

Phosphorylation of K(ATP) channels by protein kinase A (PKA) or protein kinase C (PKC) results in the modulation of channelCited by: Abbreviations: ABC protein, ATP-binding cassette protein; DMSO, dimethyl sulfoxide; K-ATP channel, ATP-sensitive potassium chan-nel; KCO, potassium channel opener.

*To whom reprint requests should be addressed. e-mail: [email protected] Downloaded at Microsoft Corporation on April 5, Cited by: Karnail S. Atwal, Advances in the structure‐activity relationships, mechanisms of action, and therapeutic utilities of ATP‐sensitive potassium channel openers, Drug Development Research, /ddr, 33, 3, (), ().

Abstract. This investigation used a patch clamp technique to test the hypothesis that protein kinase G (PKG) contributes to the phosphorylation and activation of ATP-sensitive K + (K ATP) channels in rabbit ventricular oxide donors and PKG activators facilitated pinacidil-induced K ATP channel activities in a concentration-dependent manner, and a selective PKG inhibitor.

The ATP-sensitive potassium (K atp) channel couples cellular metabolic status to changes in transmembrane potassium fluxes and cell excitability (AshcroftBabenko et al ), due to its sensitivity to intracellular ATP (leading to inhibition) and MgADP (leading to stimulation).The K atp channel is an octamer (Babenko et al., ), composed of four pore-forming α subunits (inwardly.

ATP-sensitive potassium (K(ATP)) channels are inhibited by ATP and activated by phosphatidylinositol 4,5-bisphosphate (PIP(2)). Both channel subunits Kir and sulfonylurea receptor 1 (SUR1).

In animal cells, ATP binding cassette (ABC) proteins are a large family of transporters that includes the sulfonylurea receptor and the cystic fibrosis transmembrane conductance regulator (CFTR). These two ABC proteins possess an ion channel activity and bind specific sulfonylureas, such as glibenclamide, but homologs have not been identified in plant cells.

Background: Proteins that belong to the ATP-binding cassette superfamily include transporters that mediate the efflux of substrates from cells. Among these exporters, P-glycoprotein and MRP1 are involved in cancer multidrug resistance, protection from endo and xenobiotics, determination of drug pharmacokinetics, and the pathophysiology of a.

ATP-sensitive potassium (K ATP) 1 channels are widely distributed, being found in pancreatic B-cells, cardiac, smooth, and skeletal muscles, and neurones ().They play important functional roles in all these tissues by linking cellular metabolism to electrical activity.

Opening of the K ATP channel produces a voltage-independent K + current that hyperpolarizes the cell and reduces its.

In the inside-out single-channel recordings, elevation of the Ca(2+) concentration inside the membrane from 10 nM microM decreased K(ATP) activity only in the presence of ATP. The affinity of ATP to K(ATP) became times higher with the higher concentration of Ca(2+).

Catherine A. Christian, in Hormones, Brain and Behavior (Third Edition), ATP-Sensitive Potassium Currents.

ATP-sensitive potassium currents (K ATP currents) may be of interest in regard to metabolic and hormonal regulation of GnRH neurons. These channels are closed upon elevations in intracellular ATP levels, resulting in membrane depolarization.

Abstract. The ATP-sensitive potassium (K ATP) channel plays a crucial role in insulin secretion and thus glucose homeostasis.K ATP channel activity in the pancreatic β-cell is finely balanced; increased activity prevents insulin secretion, whereas reduced activity stimulates insulin release.

The β-cell metabolism tightly regulates K ATP channel gating, and if this coupling is. rectifier potassium channel (Kir6.x) subunits and four sulfo-nylureareceptor(SURx)subunits(Aguilar-Bryanetal.,). There are two isoforms of inward rectifier potassium channel Kir and Kir (Clement et al., ).

The sulfonylurea receptor is an enzymatic member of the ABC (ATP-binding cassette) superfamily, which uses the energy of ATP bind. ATP-sensitive potassium channels; outward potassium channels; ATP-binding cassette; stomata; The ATP-binding cassette (ABC) superfamily is probably the largest and most diverse family of proteins that mediate ATP-dependent transfer of solutes.

More than ABC transporters have been identified in species ranging from Escherichia coli to human. Sulfonylurea receptors SUR1 and SUR2 are the regulatory subunits of K ATP channels. Their differential affinity for hypoglycemic sulfonylureas provides a basis for the selectivity of these compounds for different K ATP channel isoforms.

Sulfonylureas have a to fold greater affinity for SUR1 vs. SUR2. Structure-activity studies suggested a bipartite binding pocket.

Lorenz E, Alekseev AE, Krapivinsky GP, Carrasco AJ, Clapham DE, Terzic A. Evidence for direct physical interaction between a K ATP channel (Kir) and an ATP-binding cassette protein (SUR1) which affects cellular distribution and kinetic behavior of an ATP-sensitive K + channel.

Mol Cell Biol – PubMed Google Scholar. SUR associates with one of the Kir6.x potassium channel subunits to form ATP-sensitive potassium channels (K ATP). 66 This represents a unique function among the ABC family of proteins.

Unlike other atypical ABC proteins, SUR has maintained its transmembrane domain but is not thought to be directly involved in the transport of molecules across. Alejandro M. Barbieri's 6 research works with citations and reads, including: Sonic activation of molecularly-targeted nanoparticles accelerates transmembrane lipid delivery to cancer.

Introduction. Potassium channels set the cell membrane potential, generate electrical signals in excitable cells, regulate cell volume and cell movement, and support net K + transport across epithelia.

The movement of K + ions through these channels is governed by conformational changes resulting in channel opening or closing, that is, gating (Jiang et al, b; Enkvetchakul and Nichols. Congenital hyperinsulinism (CHI) is a disease characterized by persistent insulin secretion despite severe hypoglycemia.

Mutations in the pancreatic ATP-sensitive K+ (KATP) channel proteins sulfonylurea receptor 1 (SUR1) and Kir, encoded by ABCC8 and KCNJ11, respectively, is the most common cause of the disease. Many mutations in SUR1 render the channel unable to traffic to the cell. Dose- and time-dependent effects of polysulfide salt, sodium tetrasulfide (Na 2 S 4) on glucose-stimulated insulin secretion in MIN6 cells.(a,b) Mouse MIN6 cells .