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 Membr Biol
2006 Jan 01;2133:155-64. doi: 10.1007/s00232-006-0038-x.
Show Gene links
Show Anatomy links
Kir6.2 channel gating by intracellular protons: subunit stoichiometry for ligand binding and channel gating.
Wang R
,
Su J
,
Zhang X
,
Shi Y
,
Cui N
,
Onyebuchi VA
,
Jiang C
.
???displayArticle.abstract???
The adenosine triphosphate-sensitive K(+) (K(ATP)) channels are gated by several metabolites, whereas the gating mechanism remains unclear. Kir6.2, a pore-forming subunit of the K(ATP) channels, has all machineries for ligand binding and channel gating. In Kir6.2, His175 is the protonation site and Thr71 and Cys166 are involved in channel gating. Here, we show how individual subunits act in proton binding and channel gating by selectively disrupting functional subunits using these residues. All homomeric dimers and tetramers showed pH sensitivity similar to the monomeric channels. Concatenated construction of wild type with disrupted subunits revealed that none of these residues had a dominant-negative effect on the proton-dependent channel gating. Subunit action in proton binding was almost identical to that for channel gating involving Cys166, suggesting a one-to-one coupling from the C terminus to the M2 helix. This was significantly different from the effect of T71Y heteromultimers, suggesting distinct contributions of M1 and M2 helices to channel gating. Subunits underwent concerted rather than independent action. Two wild-type subunits appeared to act as a functional dimer in both cis and trans configurations. The understanding of K(ATP) channel gating by intracellular pH has a profound impact on cellular responses to metabolic stress as a significant drop in intracellular pH is more frequently seen under a number of physiological and pathophysiological conditions than a sole decrease in intracellular ATP levels.
Ashcroft,
Correlating structure and function in ATP-sensitive K+ channels.
1998, Pubmed
Ashcroft,
Correlating structure and function in ATP-sensitive K+ channels.
1998,
Pubmed
Cui,
A threonine residue (Thr71) at the intracellular end of the M1 helix plays a critical role in the gating of Kir6.2 channels by intracellular ATP and protons.
2003,
Pubmed
,
Xenbase
Davies,
Modulation of ATP-sensitive K+ channels in skeletal muscle by intracellular protons.
1990,
Pubmed
Davies,
The flickery block of ATP-dependent potassium channels of skeletal muscle by internal 4-aminopyridine.
1991,
Pubmed
Drain,
Concerted gating mechanism underlying KATP channel inhibition by ATP.
2004,
Pubmed
,
Xenbase
Drain,
KATP channel inhibition by ATP requires distinct functional domains of the cytoplasmic C terminus of the pore-forming subunit.
1998,
Pubmed
,
Xenbase
Fakler,
Identification of a titratable lysine residue that determines sensitivity of kidney potassium channels (ROMK) to intracellular pH.
1996,
Pubmed
,
Xenbase
HODGKIN,
A quantitative description of membrane current and its application to conduction and excitation in nerve.
1952,
Pubmed
Hughes,
Cloning and functional expression of human retinal kir2.4, a pH-sensitive inwardly rectifying K(+) channel.
2000,
Pubmed
,
Xenbase
Li,
Single nucleotide polymorphisms in K(ATP) channels: muscular impact on type 2 diabetes.
2005,
Pubmed
Liu,
Constraining ligand-binding site stoichiometry suggests that a cyclic nucleotide-gated channel is composed of two functional dimers.
1998,
Pubmed
Meera,
Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus.
1997,
Pubmed
Minor,
The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel.
2000,
Pubmed
,
Xenbase
MONOD,
ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL.
1965,
Pubmed
Pessia,
Differential pH sensitivity of Kir4.1 and Kir4.2 potassium channels and their modulation by heteropolymerisation with Kir5.1.
2001,
Pubmed
,
Xenbase
Piao,
Requirement of multiple protein domains and residues for gating K(ATP) channels by intracellular pH.
2001,
Pubmed
,
Xenbase
Qu,
Gating of inward rectifier K+ channels by proton-mediated interactions of N- and C-terminal domains.
2000,
Pubmed
,
Xenbase
Santa,
ATP-sensitive potassium channels mediate dilatation of basilar artery in response to intracellular acidification in vivo.
2003,
Pubmed
Schulte,
pH gating of ROMK (K(ir)1.1) channels: control by an Arg-Lys-Arg triad disrupted in antenatal Bartter syndrome.
1999,
Pubmed
Seino,
ATP-sensitive potassium channels: a model of heteromultimeric potassium channel/receptor assemblies.
1999,
Pubmed
Trapp,
Molecular analysis of ATP-sensitive K channel gating and implications for channel inhibition by ATP.
1998,
Pubmed
,
Xenbase
Tsai,
Intracellular H+ inhibits a cloned rat kidney outer medulla K+ channel expressed in Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Tucker,
Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor.
1997,
Pubmed
,
Xenbase
Tucker,
Mapping of the physical interaction between the intracellular domains of an inwardly rectifying potassium channel, Kir6.2.
1999,
Pubmed
Ulens,
Regulation of hyperpolarization-activated HCN channels by cAMP through a gating switch in binding domain symmetry.
2003,
Pubmed
,
Xenbase
Varnum,
Interdomain interactions underlying activation of cyclic nucleotide-gated channels.
1997,
Pubmed
,
Xenbase
Wang,
Hypercapnic acidosis activates KATP channels in vascular smooth muscles.
2003,
Pubmed
Wang,
Subunit stoichiometry of the Kir1.1 channel in proton-dependent gating.
2005,
Pubmed
,
Xenbase
Wang,
Determinant role of membrane helices in K ATP channel gating.
2005,
Pubmed
,
Xenbase
Wu,
Allosteric modulation of the mouse Kir6.2 channel by intracellular H+ and ATP.
2002,
Pubmed
,
Xenbase
Wu,
Critical protein domains and amino acid residues for gating the KIR6.2 channel by intracellular ATP.
2004,
Pubmed
Xu,
Distinct histidine residues control the acid-induced activation and inhibition of the cloned K(ATP) channel.
2001,
Pubmed
,
Xenbase
Xu,
Modulation of kir4.1 and kir5.1 by hypercapnia and intracellular acidosis.
2000,
Pubmed
,
Xenbase
Xu,
Direct activation of cloned K(atp) channels by intracellular acidosis.
2001,
Pubmed
,
Xenbase
Yang,
Opposite effects of pH on open-state probability and single channel conductance of kir4.1 channels.
1999,
Pubmed
,
Xenbase
Yang,
Biophysical and molecular mechanisms underlying the modulation of heteromeric Kir4.1-Kir5.1 channels by CO2 and pH.
2000,
Pubmed
,
Xenbase
Zhu,
CO(2) inhibits specific inward rectifier K(+) channels by decreases in intra- and extracellular pH.
2000,
Pubmed
,
Xenbase
