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.
???displayArticle.abstract???
The objective of the present study was to clarify the mechanism by which the sulfonylurea drug, glibenclamide, inhibits single CFTR channels in excised patches from Xenopus oocytes. Glibenclamide blocks the open pore of the channel via binding at multiple sites with varying kinetics. In the absence of glibenclamide, open-channel bursts exhibited a flickery intraburst closed state (C1); this is due to block of the pore by the pH buffer, TES. Application of 25 microM glibenclamide to the cytoplasmic solution resulted in the appearance of two drug-induced intraburst closed states (C2, C3) of widely different duration, which differed in pH-dependence. The kinetics of interaction with the C3 state, but not the C2 state, were strongly voltage-dependent. The durations of both the C2 and C3 states were concentration-dependent, indicating a non-linear reaction scheme. Application of drug also increased the burst duration, which is consistent with an open-channel blocking mechanism. A kinetic model is proposed. These results indicate that glibenclamide interacts with open CFTR channels in a complex manner, involving interactions with multiple binding sites in the channel pore.
Aguilar-Bryan,
Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.
1995, Pubmed
Aguilar-Bryan,
Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.
1995,
Pubmed
Anderson,
Generation of cAMP-activated chloride currents by expression of CFTR.
1991,
Pubmed
Ashfield,
Identification of the high-affinity tolbutamide site on the SUR1 subunit of the K(ATP) channel.
1999,
Pubmed
,
Xenbase
Babenko,
The tolbutamide site of SUR1 and a mechanism for its functional coupling to K(ATP) channel closure.
1999,
Pubmed
Bear,
Purification and functional reconstitution of the cystic fibrosis transmembrane conductance regulator (CFTR).
1992,
Pubmed
Cai,
Inhibition of heterologously expressed cystic fibrosis transmembrane conductance regulator Cl- channels by non-sulphonylurea hypoglycaemic agents.
1999,
Pubmed
Cai,
Voltage-dependent gating of the cystic fibrosis transmembrane conductance regulator Cl- channel.
2003,
Pubmed
Fischer,
CFTR displays voltage dependence and two gating modes during stimulation.
1994,
Pubmed
Giblin,
The cytoplasmic C-terminus of the sulfonylurea receptor is important for KATP channel function but is not key for complex assembly or trafficking.
2002,
Pubmed
Golstein,
P-glycoprotein inhibition by glibenclamide and related compounds.
1999,
Pubmed
Gupta,
Point mutations in the pore region directly or indirectly affect glibenclamide block of the CFTR chloride channel.
2002,
Pubmed
Hanrahan,
Inhibition of an outwardly rectifying anion channel by HEPES and related buffers.
1990,
Pubmed
Haws,
CFTR channels in immortalized human airway cells.
1992,
Pubmed
Ishihara,
Block by MOPS reveals a conformation change in the CFTR pore produced by ATP hydrolysis.
1997,
Pubmed
Julien,
Cystic fibrosis transmembrane conductance regulator (CFTR) confers glibenclamide sensitivity to outwardly rectifying chloride channel (ORCC) in Hi-5 insect cells.
1999,
Pubmed
Linsdell,
Disulphonic stilbene block of cystic fibrosis transmembrane conductance regulator Cl- channels expressed in a mammalian cell line and its regulation by a critical pore residue.
1996,
Pubmed
Luo,
Differential regulation of single CFTR channels by PP2C, PP2A, and other phosphatases.
1998,
Pubmed
Mathews,
Dibasic protein kinase A sites regulate bursting rate and nucleotide sensitivity of the cystic fibrosis transmembrane conductance regulator chloride channel.
1998,
Pubmed
McCarty,
Voltage-dependent block of the cystic fibrosis transmembrane conductance regulator Cl- channel by two closely related arylaminobenzoates.
1993,
Pubmed
,
Xenbase
McCarty,
Permeation through the CFTR chloride channel.
2000,
Pubmed
McDonough,
Novel pore-lining residues in CFTR that govern permeation and open-channel block.
1994,
Pubmed
McNicholas,
Sensitivity of a renal K+ channel (ROMK2) to the inhibitory sulfonylurea compound glibenclamide is enhanced by coexpression with the ATP-binding cassette transporter cystic fibrosis transmembrane regulator.
1996,
Pubmed
,
Xenbase
Mehnert,
[Glybenclamide (HB 419): a new oral antidiabetic agent of the sulfonylurea group].
1969,
Pubmed
Mikhailov,
Molecular structure of the glibenclamide binding site of the beta-cell K(ATP) channel.
2001,
Pubmed
Neher,
Local anaesthetics transiently block currents through single acetylcholine-receptor channels.
1978,
Pubmed
Ogden,
Ion channel block by acetylcholine, carbachol and suberyldicholine at the frog neuromuscular junction.
1985,
Pubmed
Okuno,
Effect of tolbutamide and glyburide on cAMP-dependent protein kinase activity in rat liver cytosol.
1988,
Pubmed
Quick,
Incubation with horse serum increases viability and decreases background neurotransmitter uptake in Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Rabe,
Cl- channel inhibition by glibenclamide is not specific for the CFTR-type Cl- channel.
1995,
Pubmed
Riordan,
Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
1989,
Pubmed
Schultz,
Glibenclamide blockade of CFTR chloride channels.
1996,
Pubmed
Schwiebert,
CFTR is a conductance regulator as well as a chloride channel.
1999,
Pubmed
Sheppard,
Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents.
1992,
Pubmed
Sheppard,
Mechanism of glibenclamide inhibition of cystic fibrosis transmembrane conductance regulator Cl- channels expressed in a murine cell line.
1997,
Pubmed
Sturgess,
The sulphonylurea receptor may be an ATP-sensitive potassium channel.
1985,
Pubmed
Walsh,
Structural and ionic determinants of 5-nitro-2-(3-phenylprophyl-amino)-benzoic acid block of the CFTR chloride channel.
1999,
Pubmed
,
Xenbase
Weinreich,
Dual effects of ADP and adenylylimidodiphosphate on CFTR channel kinetics show binding to two different nucleotide binding sites.
1999,
Pubmed
,
Xenbase
Winter,
Effect of ATP concentration on CFTR Cl- channels: a kinetic analysis of channel regulation.
1994,
Pubmed
Woodhull,
Ionic blockage of sodium channels in nerve.
1973,
Pubmed
Yamazaki,
Inhibitory effects of glibenclamide on cystic fibrosis transmembrane regulator, swelling-activated, and Ca(2+)-activated Cl- channels in mammalian cardiac myocytes.
1997,
Pubmed
Zeltwanger,
Gating of cystic fibrosis transmembrane conductance regulator chloride channels by adenosine triphosphate hydrolysis. Quantitative analysis of a cyclic gating scheme.
1999,
Pubmed
Zhang,
Voltage-sensitive gating induced by a mutation in the fifth transmembrane domain of CFTR.
2002,
Pubmed
,
Xenbase
Zhang,
Direct comparison of NPPB and DPC as probes of CFTR expressed in Xenopus oocytes.
2000,
Pubmed
,
Xenbase
Zhou,
Voltage-dependent flickery block of an open cystic fibrosis transmembrane conductance regulator (CFTR) channel pore.
2001,
Pubmed
Zhou,
Probing an open CFTR pore with organic anion blockers.
2002,
Pubmed
Zhu,
Association of cystic fibrosis transmembrane conductance regulator and protein phosphatase 2C.
1999,
Pubmed
