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
2006 Feb 15;571Pt 1:3-14. doi: 10.1113/jphysiol.2005.099168.
Show Gene links
Show Anatomy links
Functional effects of naturally occurring KCNJ11 mutations causing neonatal diabetes on cloned cardiac KATP channels.
Tammaro P
,
Proks P
,
Ashcroft FM
.
???displayArticle.abstract???
ATP-sensitive K+ (K(ATP)) channels are hetero-octamers of inwardly rectifying K+ channel (Kir6.2) and sulphonylurea receptor subunits (SUR1 in pancreatic beta-cells, SUR2A in heart). Heterozygous gain-of-function mutations in Kir6.2 cause neonatal diabetes, which may be accompanied by epilepsy and developmental delay. However, despite the importance of K(ATP) channels in the heart, patients have no obvious cardiac problems. We examined the effects of adenine nucleotides on K(ATP) channels containing wild-type or mutant (Q52R, R201H) Kir6.2 plus either SUR1 or SUR2A. In the absence of Mg2+, both mutations reduced ATP inhibition of SUR1- and SUR2A-containing channels to similar extents, but when Mg2+ was present ATP blocked mutant channels containing SUR1 much less than SUR2A channels. Mg-nucleotide activation of SUR1, but not SUR2A, channels was markedly increased by the R201H mutation. Both mutations also increased resting whole-cell K(ATP) currents through heterozygous SUR1-containing channels to a greater extent than for heterozygous SUR2A-containing channels. The greater ATP inhibition of mutant Kir6.2/SUR2A than of Kir6.2/SUR1 can explain why gain-of-function Kir6.2 mutations manifest effects in brain and beta-cells but not in the heart.
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
Allen,
Modulation of the excitability of cholinergic basal forebrain neurones by KATP channels.
2004,
Pubmed
Antcliff,
Functional analysis of a structural model of the ATP-binding site of the KATP channel Kir6.2 subunit.
2005,
Pubmed
Ashcroft,
ATP-sensitive potassium channelopathies: focus on insulin secretion.
2005,
Pubmed
Ashcroft,
Correlating structure and function in ATP-sensitive K+ channels.
1998,
Pubmed
Ashcroft,
Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells.
,
Pubmed
Babenko,
Reconstituted human cardiac KATP channels: functional identity with the native channels from the sarcolemma of human ventricular cells.
1998,
Pubmed
Babenko,
The N-terminus of KIR6.2 limits spontaneous bursting and modulates the ATP-inhibition of KATP channels.
1999,
Pubmed
Chan,
N-terminal transmembrane domain of the SUR controls trafficking and gating of Kir6 channel subunits.
2003,
Pubmed
,
Xenbase
Clement,
Association and stoichiometry of K(ATP) channel subunits.
1997,
Pubmed
Deist,
Sulfonylurea-sensitive K+ channels and their probable role for the membrane potential of mouse motor nerve endings.
1992,
Pubmed
Enkvetchakul,
The kinetic and physical basis of K(ATP) channel gating: toward a unified molecular understanding.
2000,
Pubmed
Gloyn,
Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes.
2004,
Pubmed
,
Xenbase
Gribble,
Properties of cloned ATP-sensitive K+ currents expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Gribble,
MgATP activates the beta cell KATP channel by interaction with its SUR1 subunit.
1998,
Pubmed
,
Xenbase
Gribble,
Tissue specificity of sulfonylureas: studies on cloned cardiac and beta-cell K(ATP) channels.
1998,
Pubmed
,
Xenbase
Gribble,
Sulphonylurea action revisited: the post-cloning era.
2003,
Pubmed
Gumina,
Knockout of Kir6.2 negates ischemic preconditioning-induced protection of myocardial energetics.
2003,
Pubmed
Hattersley,
Activating mutations in Kir6.2 and neonatal diabetes: new clinical syndromes, new scientific insights, and new therapy.
2005,
Pubmed
Inagaki,
A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels.
1996,
Pubmed
Inagaki,
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.
1995,
Pubmed
Isomoto,
A novel sulfonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K+ channel.
1996,
Pubmed
John,
Molecular mechanism for ATP-dependent closure of the K+ channel Kir6.2.
2003,
Pubmed
Koster,
Tolerance for ATP-insensitive K(ATP) channels in transgenic mice.
2001,
Pubmed
Langheinrich,
Hyperpolarization of isolated capillaries from guinea-pig heart induced by K+ channel openers and glucose deprivation.
1997,
Pubmed
Lee,
The high-affinity sulphonylurea receptor regulates KATP channels in nerve terminals of the rat motor cortex.
1996,
Pubmed
Masia,
Differential nucleotide regulation of KATP channels by SUR1 and SUR2A.
2005,
Pubmed
Matsuo,
Different binding properties and affinities for ATP and ADP among sulfonylurea receptor subtypes, SUR1, SUR2A, and SUR2B.
2000,
Pubmed
Matsuoka,
C-terminal tails of sulfonylurea receptors control ADP-induced activation and diazoxide modulation of ATP-sensitive K(+) channels.
2000,
Pubmed
Miki,
ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis.
2001,
Pubmed
Morrissey,
Immunolocalization of KATP channel subunits in mouse and rat cardiac myocytes and the coronary vasculature.
2005,
Pubmed
Nichols,
Adenosine diphosphate as an intracellular regulator of insulin secretion.
1996,
Pubmed
Nichols,
Adenosine triphosphate-sensitive potassium channels in the cardiovascular system.
1991,
Pubmed
Proks,
Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features.
2004,
Pubmed
,
Xenbase
Rainbow,
SUR2A C-terminal fragments reduce KATP currents and ischaemic tolerance of rat cardiac myocytes.
2004,
Pubmed
Sagen,
Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy.
2004,
Pubmed
Sakura,
Cloning and functional expression of the cDNA encoding a novel ATP-sensitive potassium channel subunit expressed in pancreatic beta-cells, brain, heart and skeletal muscle.
1995,
Pubmed
Seino,
Physiological and pathophysiological roles of ATP-sensitive K+ channels.
2003,
Pubmed
Suzuki,
Role of sarcolemmal K(ATP) channels in cardioprotection against ischemia/reperfusion injury in mice.
2002,
Pubmed
Tammaro,
Kir6.2 mutations causing neonatal diabetes provide new insights into Kir6.2-SUR1 interactions.
2005,
Pubmed
,
Xenbase
Trapp,
Activation and inhibition of K-ATP currents by guanine nucleotides is mediated by different channel subunits.
1997,
Pubmed
,
Xenbase
Trapp,
Molecular analysis of ATP-sensitive K channel gating and implications for channel inhibition by ATP.
1998,
Pubmed
,
Xenbase
Tucker,
Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor.
1997,
Pubmed
,
Xenbase
Tucker,
Molecular determinants of KATP channel inhibition by ATP.
1998,
Pubmed
,
Xenbase
Wang,
The regulation of glucose-excited neurons in the hypothalamic arcuate nucleus by glucose and feeding-relevant peptides.
2004,
Pubmed
Zingman,
Tandem function of nucleotide binding domains confers competence to sulfonylurea receptor in gating ATP-sensitive K+ channels.
2002,
Pubmed
Zingman,
Kir6.2 is required for adaptation to stress.
2002,
Pubmed
