Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Physiol
2004 Aug 15;559Pt 1:157-67. doi: 10.1113/jphysiol.2004.065094.
Show Gene links
Show Anatomy links
Zinc is both an intracellular and extracellular regulator of KATP channel function.
Prost AL
,
Bloc A
,
Hussy N
,
Derand R
,
Vivaudou M
.
???displayArticle.abstract???
Extracellular Zn(2+) has been identified as an activator of pancreatic K(ATP) channels. We further examined the action of Zn(2+) on recombinant K(ATP) channels formed with the inward rectifier K(+) channel subunit Kir6.2 associated with either the pancreatic/neuronal sulphonylurea receptor 1 (SUR1) subunit or the cardiac SUR2A subunit. Zn(2+), applied at either the extracellular or intracellular side of the membrane appeared as a potent, reversible activator of K(ATP) channels. External Zn(2+), at micromolar concentrations, activated SUR1/Kir6.2 but induced a small inhibition of SUR2A/Kir6.2 channels. Cytosolic Zn(2+) dose-dependently stimulated both SUR1/Kir6.2 and SUR2A/Kir6.2 channels, with half-maximal effects at 1.8 and 60 microm, respectively, but it did not affect the Kir6.2 subunit expressed alone. These observations point to an action of both external and internal Zn(2+) on the SUR subunit. Effects of internal Zn(2+) were not due to Zn(2+) leaking out, since they were unaffected by the presence of a Zn(2+) chelator on the external side. Similarly, internal chelators did not affect activation by external Zn(2+). Therefore, Zn(2+) is an endogenous K(ATP) channel opener being active on both sides of the membrane, with potentially distinct sites of action located on the SUR subunit. These findings uncover a novel regulatory pathway targeting K(ATP) channels, and suggest a new role for Zn(2+) as an intracellular signalling molecule.
Ashcroft,
Properties and functions of ATP-sensitive K-channels.
1990, Pubmed
Ashcroft,
Properties and functions of ATP-sensitive K-channels.
1990,
Pubmed
Aspinwall,
Effects of intravesicular H+ and extracellular H+ and Zn2+ on insulin secretion in pancreatic beta cells.
1997,
Pubmed
Aspinwall,
Insulin-stimulated insulin secretion in single pancreatic beta cells.
1999,
Pubmed
Atar,
Excitation-transcription coupling mediated by zinc influx through voltage-dependent calcium channels.
1995,
Pubmed
Beyersmann,
Functions of zinc in signaling, proliferation and differentiation of mammalian cells.
2001,
Pubmed
Bloc,
Zinc-induced changes in ionic currents of clonal rat pancreatic -cells: activation of ATP-sensitive K+ channels.
2000,
Pubmed
Cai,
Nucleotide binding and nucleotide hydrolysis properties of the ABC transporter MRP6 (ABCC6).
2002,
Pubmed
Cook,
ATP-sensitive K+ channels in pancreatic beta-cells. Spare-channel hypothesis.
1988,
Pubmed
D'hahan,
A transmembrane domain of the sulfonylurea receptor mediates activation of ATP-sensitive K(+) channels by K(+) channel openers.
1999,
Pubmed
,
Xenbase
D'hahan,
Pharmacological plasticity of cardiac ATP-sensitive potassium channels toward diazoxide revealed by ADP.
1999,
Pubmed
,
Xenbase
Dodson,
The role of assembly in insulin's biosynthesis.
1998,
Pubmed
Ferrer,
Effects of Zn2+ on glucose-induced electrical activity and insulin release from mouse pancreatic islets.
1984,
Pubmed
Forestier,
Mechanism of action of K channel openers on skeletal muscle KATP channels. Interactions with nucleotides and protons.
1996,
Pubmed
Frederickson,
Synaptically released zinc: physiological functions and pathological effects.
2001,
Pubmed
Gaither,
Eukaryotic zinc transporters and their regulation.
2001,
Pubmed
Ghafghazi,
Zinc-induced inhibition of insulin secretion from isolated rat islets of Langerhans.
1981,
Pubmed
Gribble,
MgATP activates the beta cell KATP channel by interaction with its SUR1 subunit.
1998,
Pubmed
,
Xenbase
Hantke,
Bacterial zinc transporters and regulators.
2001,
Pubmed
Harrison,
Zn2+: an endogenous modulator of ligand- and voltage-gated ion channels.
1994,
Pubmed
Hershfinkel,
A zinc-sensing receptor triggers the release of intracellular Ca2+ and regulates ion transport.
2001,
Pubmed
Huang,
Metal ions and synaptic transmission: think zinc.
1997,
Pubmed
Ishihara,
Islet beta-cell secretion determines glucagon release from neighbouring alpha-cells.
2003,
Pubmed
Jia,
Zn2+ currents are mediated by calcium-permeable AMPA/kainate channels in cultured murine hippocampal neurones.
2002,
Pubmed
Kakei,
Receptor-operated regulation of ATP-sensitive K+ channels via membrane phospholipid metabolism.
2003,
Pubmed
Kerchner,
Zn2+ current is mediated by voltage-gated Ca2+ channels and enhanced by extracellular acidity in mouse cortical neurones.
2000,
Pubmed
Kim,
Zinc as a paracrine effector in pancreatic islet cell death.
2000,
Pubmed
Kwok,
Block of cardiac ATP-sensitive K+ channels by external divalent cations is modulated by intracellular ATP. Evidence for allosteric regulation of the channel protein.
1993,
Pubmed
Li,
Rapid translocation of Zn(2+) from presynaptic terminals into postsynaptic hippocampal neurons after physiological stimulation.
2001,
Pubmed
Li,
A new pathway for vacuolar cadmium sequestration in Saccharomyces cerevisiae: YCF1-catalyzed transport of bis(glutathionato)cadmium.
1997,
Pubmed
Light,
Molecular basis of protein kinase C-induced activation of ATP-sensitive potassium channels.
2000,
Pubmed
Light,
Regulation of ATP-sensitive potassium channels by phosphorylation.
1996,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Lin,
Zinc-induced augmentation of excitatory synaptic currents and glutamate receptor responses in hippocampal CA3 neurons.
2001,
Pubmed
Maret,
Crosstalk of the group IIa and IIb metals calcium and zinc in cellular signaling.
2001,
Pubmed
Miledi,
Membrane currents elicited by divalent cations in Xenopus oocytes.
1989,
Pubmed
,
Xenbase
Monteilh-Zoller,
TRPM7 provides an ion channel mechanism for cellular entry of trace metal ions.
2003,
Pubmed
Moreau,
The molecular basis of the specificity of action of K(ATP) channel openers.
2000,
Pubmed
Ragozzino,
Zinc permeates mouse muscle ACh receptor channels expressed in BOSC 23 cells and affects channel function.
2000,
Pubmed
Seino,
Physiological and pathophysiological roles of ATP-sensitive K+ channels.
2003,
Pubmed
Sensi,
Measurement of intracellular free zinc in living cortical neurons: routes of entry.
1997,
Pubmed
Sheline,
Depolarization-induced 65zinc influx into cultured cortical neurons.
2002,
Pubmed
Shibasaki,
Interaction of ATP sensor, cAMP sensor, Ca2+ sensor, and voltage-dependent Ca2+ channel in insulin granule exocytosis.
2004,
Pubmed
Smart,
Modulation of inhibitory and excitatory amino acid receptor ion channels by zinc.
1994,
Pubmed
Standen,
Cardioprotection by preconditioning: K(ATP) channels, metabolism, or both?
2002,
Pubmed
Tabata,
A zinc-dependent Cl- current in neuronal somata.
1999,
Pubmed
Tommasini,
The human multidrug resistance-associated protein functionally complements the yeast cadmium resistance factor 1.
1996,
Pubmed
Tucker,
Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor.
1997,
Pubmed
,
Xenbase
Vallee,
The biochemical basis of zinc physiology.
1993,
Pubmed
Vivaudou,
Skeletal muscle ATP-sensitive K+ channels recorded from sarcolemmal blebs of split fibers: ATP inhibition is reduced by magnesium and ADP.
1991,
Pubmed
Vivaudou,
Modification by protons of frog skeletal muscle KATP channels: effects on ion conduction and nucleotide inhibition.
1995,
Pubmed
Wang,
Inhibition of ryanodine binding to sarcoplasmic reticulum vesicles of cardiac muscle by Zn(2+) ions.
2001,
Pubmed
Weiss,
Zn(2+): a novel ionic mediator of neural injury in brain disease.
2000,
Pubmed
Xie,
Phospholipase C-linked receptors regulate the ATP-sensitive potassium channel by means of phosphatidylinositol 4,5-bisphosphate metabolism.
1999,
Pubmed
Zerangue,
A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels.
1999,
Pubmed
,
Xenbase
