CoChat
Sign Up
Cited by 11Ion channel regulation and functionAdenosine and Purinergic SignalingIon Transport and Channel Regulation

Running out of time: the decline of channel activity and nucleotide activation in adenosine triphosphate-sensitive K-channels

Open access
Proks, Peter, Puljung, Michael C., Vedovato, Natascia, Sachse, Gregor, Mulvaney, Rachel, Ashcroft, Frances M.·2016·Philosophical Transactions of the Royal Society B: Biological Sciences
DOI 10.1098/rstb.2015.0426PMC PMC4938026
Open this paper in CoChat — free account

Abstract

K ATP channels act as key regulators of electrical excitability by coupling metabolic cues—mainly intracellular adenine nucleotide concentrations—to cellular potassium ion efflux. However, their study has been hindered by their rapid loss of activity in excised membrane patches (rundown), and by a second phenomenon, the d ecline of a ctivation by M g- n ucleotides (DAMN). Degradation of PI(4,5)P 2 and other phosphoinositides is the strongest candidate for the molecular cause of rundown. Broad evidence indicates that most other determinants of rundown (e.g. phosphorylation, intracellular calcium, channel mutations that affect rundown) also act by influencing K ATP channel regulation by phosphoinositides. Unfortunately, experimental conditions that reproducibly prevent rundown have remained elusive, necessitating post hoc data compensation. Rundown is clearly distinct from DAMN. While the former is associated with pore-forming Kir6.2 subunits, DAMN is generally a slower process involving the regulatory sulfonylurea receptor (SUR) subunits. We speculate that it arises when SUR subunits enter non-physiological conformational states associated with the loss of SUR nucleotide-binding domain dimerization following prolonged exposure to nucleotide-free conditions. This review presents new information on both rundown and DAMN, summarizes our current understanding of these processes and considers their physiological roles. This article is part of the themed issue ‘Evolution brings Ca 2+ and ATP together to control life and death’.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1098/rstb.2015.0426

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The number of KATP channels per β-cell is not known with certainty because open probability varies with measurement conditions.

    “However, the open probability varies considerably according to how it is measured: in cell-attached patches it varies with the intracellular ATP concentration, while in inside-out patches it diminishes with time after patch excision (rundown; (526). Accordingly, the number of KATP channels per β-cell is not known with certainty.”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [526]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 61

  1. [1]Miki T, Seino S 2005 Roles of KATP channels as metabolic sensors in acute metabolic changes. J. Mol. Cell. Cardiol. 38, 917– 925. (10.1016/j.yjmcc.2004.11.019) 15910876 · DOI
  2. [3]Nichols CG, Shyng SL, Nestorowicz A, Glaser B, Clement JP, Gonzalez G, Aguilar-Bryan L, Permutt MA, Bryan J 1996 Adenosine diphosphate as an intracellular regulator of insulin secretion. Science 272, 1785– 1787. (10.1126/science.272.5269.1785) 8650576 · DOI
  3. [4]Tucker SJ, Gribble FM, Zhao C, Trapp S, Ashcroft FM 1997 Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor. Nature 387, 179– 183. (10.1038/387179a0) 9144288 · DOI
  4. [5]Gribble FM, Tucker SJ, Ashcroft FM 1997 The essential role of the Walker A motifs of SUR1 in KATP channel activation by Mg-ADP and diazoxide. EMBO J. 16, 1145– 1152. (10.1093/emboj/16.6.1145) 9135131 PMC1169713 · DOI · Paper page
  5. [6]Proks P, de Wet H, Ashcroft FM 2010 Activation of the KATP channel by Mg-nucleotide interaction with SUR1. J. Gen. Physiol. 136, 389– 405. (10.1085/jgp.201010475) 20876358 PMC2947056 · DOI · Paper page
  6. [7]Ohno-Shosaku T, Zunkler BJ, Trube G 1987 Dual effects of ATP on K+ currents of mouse pancreatic beta-cells. Pflugers Arch. 408, 133– 138. (10.1007/BF00581342) 2436138 · DOI
  7. [8]Nichols CG, Lederer WJ 1990 The regulation of ATP-sensitive K+ channel activity in intact and permeabilized rat ventricular myocytes. J. Physiol. 423, 91– 110. (10.1113/jphysiol.1990.sp018013) 2388163 PMC1189748 · DOI
  8. [9]Okuyama Y et al. 1998 The effects of nucleotides and potassium channel openers on the SUR2A/Kir6.2 complex K+ channel expressed in a mammalian cell line, HEK293 T cells. Pflugers Arch. 435, 595– 603. (10.1007/s004240050559) 9479011 · DOI
  9. [10]Ribalet B, John SA, Weiss JN 2000 Regulation of cloned ATP-sensitive K channels by phosphorylation, MgADP, and phosphatidylinositol bisphosphate (PIP2): a study of channel rundown and reactivation. J. Gen. Physiol. 116, 391– 410. (10.1085/jgp.116.3.391) 10962016 PMC2233681 · DOI
  10. [11]Drain P, Li L, Wang J 1998 KATP channel inhibition by ATP requires distinct functional domains of the cytoplasmic C terminus of the pore-forming subunit. Proc. Natl Acad. Sci. USA 95, 13 953– 13 958. (10.1073/pnas.95.23.13953) 9811907 PMC24984 · DOI
  11. [12]Proks P, Ashcroft FM 1997 Phentolamine block of KATP channels is mediated by Kir6.2. Proc. Natl Acad. Sci. USA 94, 11 716– 11 720. (10.1073/pnas.94.21.11716) 9326676 PMC23609 · DOI
  12. [13]Zerangue N, Schwappach B, Jan YN, Jan LY 1999 A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane KATP channels. Neuron 22, 537– 548. (10.1016/S0896-6273(00)80708-4) 10197533 · DOI · Paper page
  13. [14]Huang CL, Feng S, Hilgemann DW 1998 Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by gbetagamma. Nature 391, 803– 806. (10.1038/35882) 9486652 · DOI
  14. [15]Rohacs T, Lopes CM, Jin T, Ramdya PP, Molnar Z, Logothetis DE 2003 Specificity of activation by phosphoinositides determines lipid regulation of Kir channels. Proc. Natl Acad. Sci. USA 100, 745– 750. (10.1073/pnas.0236364100) 12525701 PMC141067 · DOI
  15. [16]Logothetis DE, Petrou VI, Zhang M, Mahajan R, Meng XY, Adney SK, Cui M, Baki L 2015 Phosphoinositide control of membrane protein function: a frontier led by studies on ion channels. Annu. Rev. Physiol. 77, 81– 104. (10.1146/annurev-physiol-021113-170358) 25293526 PMC4485992 · DOI
  16. [17]Hilgemann DW, Ball R 1996 Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2. Science 273, 956– 959. (10.1126/science.273.5277.956) 8688080 · DOI
  17. [18]Fan Z, Makielski JC 1997 Anionic phospholipids activate ATP-sensitive potassium channels. J. Biol. Chem. 272, 5388– 5395. (10.1074/jbc.272.9.5388) 9038137 · DOI
  18. [19]Fan Z, Makielski JC 1999 Phosphoinositides decrease ATP sensitivity of the cardiac ATP-sensitive K+ channel. A molecular probe for the mechanism of ATP-sensitive inhibition. J. Gen. Physiol. 114, 251– 269. (10.1085/jgp.114.2.251) 10436001 PMC2230641 · DOI
  19. [20]Shyng SL, Nichols CG 1998 Membrane phospholipid control of nucleotide sensitivity of KATP channels. Science 282, 1138– 1141. (10.1126/science.282.5391.1138) 9804554 · DOI · Paper page
  20. [21]Baukrowitz T, Schulte U, Oliver D, Herlitze S, Krauter T, Tucker SJ, Ruppersberg JP, Fakler B 1998 PIP2 and PIP as determinants for ATP inhibition of KATP channels. Science 282, 1141– 1144. (10.1126/science.282.5391.1141) 9804555 · DOI
  21. [22]Rjasanow A, Leitner MG, Thallmair V, Halaszovich CR, Oliver D 2015 Ion channel regulation by phosphoinositides analyzed with VSPs-PI(4,5)P2 affinity, phosphoinositide selectivity, and PI(4,5)P2 pool accessibility. Front. Pharmacol. 6, 127 (10.3389/fphar.2015.00127) 26150791 PMC4472987 · DOI
  22. [23]Wang YJ, Li WH, Wang J, Xu K, Dong P, Luo X, Yin HL 2004 Critical role of PIP5KI{gamma}87 in InsP3-mediated Ca2+ signaling. J. Cell Biol. 167, 1005– 1010. (10.1083/jcb.200408008) 15611330 PMC2172614 · DOI
  23. [24]Enkvetchakul D, Nichols CG 2003 Gating mechanism of KATP channels: function fits form. J. Gen. Physiol. 122, 471– 480. (10.1085/jgp.200308878) 14581579 PMC2229585 · DOI
  24. [25]Hansen SB, Tao X, MacKinnon R 2011 Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2. Nature 477, 495– 498. (10.1038/nature10370) 21874019 PMC3324908 · DOI
  25. [26]Antcliff JF, Haider S, Proks P, Sansom MS, Ashcroft FM 2005 Functional analysis of a structural model of the ATP-binding site of the KATP channel Kir6.2 subunit. EMBO J. 24, 229– 239. (10.1038/sj.emboj.7600487) 15650751 PMC545803 · DOI
  26. [27]Wang C, Wang K, Wang W, Cui Y, Fan Z 2002 Compromised ATP binding as a mechanism of phosphoinositide modulation of ATP-sensitive K+ channels. FEBS Lett. 532, 177– 182. (10.1016/S0014-5793(02)03671-2) 12459485 · DOI
  27. [28]MacGregor GG, Dong K, Vanoye CG, Tang L, Giebisch G, Hebert SC 2002 Nucleotides and phospholipids compete for binding to the C terminus of KATP channels. Proc. Natl Acad. Sci. USA 99, 2726– 2731. (10.1073/pnas.042688899) 11880626 PMC122415 · DOI
  28. [29]Xie LH, Horie M, Takano M 1999 Phospholipase C-linked receptors regulate the ATP-sensitive potassium channel by means of phosphatidylinositol 4,5-bisphosphate metabolism. Proc. Natl Acad. Sci. USA. 96, 15 292– 15 297. (10.1073/pnas.96.26.15292) PMC24813 10611378 · DOI
  29. [30]Gribble FM, Proks P, Corkey BE, Ashcroft FM 1998 Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA. J. Biol. Chem. 273, 26 383– 26 387. (10.1074/jbc.273.41.26383) 9756869 · DOI · Paper page
  30. [31]Schulze D, Rapedius M, Krauter T, Baukrowitz T 2003 Long-chain acyl-CoA esters and phosphatidylinositol phosphates modulate ATP inhibition of KATP channels by the same mechanism. J. Physiol. 552, 357– 367. (10.1113/jphysiol.2003.047035) 14561820 PMC2343384 · DOI
  31. [32]Rapedius M, Soom M, Shumilina E, Schulze D, Schonherr R, Kirsch C, Lang F, Tucker SJ, Baukrowitz T 2005 Long chain CoA esters as competitive antagonists of phosphatidylinositol 4,5-bisphosphate activation in Kir channels. J. Biol. Chem. 280, 30 760– 30 767. (10.1074/jbc.M503503200) 15980413 · DOI
  32. [33]Chan KW, Zhang H, Logothetis DE 2003 N-terminal transmembrane domain of the SUR controls trafficking and gating of Kir6 channel subunits. EMBO J. 22, 3833– 3843. (10.1093/emboj/cdg376) 12881418 PMC169049 · DOI
  33. [34]Babenko AP, Gonzalez G, Bryan J 1999 Two regions of sulfonylurea receptor specify the spontaneous bursting and ATP inhibition of KATP channel isoforms. J. Biol. Chem. 274, 11 587– 11 592. (10.1074/jbc.274.17.11587) 10206966 · DOI
  34. [35]Ribalet B, John SA, Xie LH, Weiss JN 2006 ATP-sensitive K+ channels: regulation of bursting by the sulphonylurea receptor, PIP2 and regions of Kir6.2. J. Physiol. 571, 303– 317. (10.1113/jphysiol.2005.100719) 16373383 PMC1796795 · DOI
  35. [36]Pratt EB, Tewson P, Bruederle CE, Skach WR, Shyng SL 2011 N-terminal transmembrane domain of SUR1 controls gating of Kir6.2 by modulating channel sensitivity to PIP2. J. Gen. Physiol. 137, 299– 314. (10.1085/jgp.201010557) 21321069 PMC3047609 · DOI
  36. [37]Lin YW, Jia T, Weinsoft AM, Shyng SL 2003 Stabilization of the activity of ATP-sensitive potassium channels by ion pairs formed between adjacent Kir6.2 subunits. J. Gen. Physiol. 122, 225– 237. (10.1085/jgp.200308822) 12885877 PMC2229541 · DOI
  37. [38]Girard CA, Shimomura K, Proks P, Absalom N, Castano L, Perez de Nanclares G, Ashcroft FM 2006 Functional analysis of six Kir6.2 (KCNJ11) mutations causing neonatal diabetes. Pflugers Arch. 453, 323– 332. (10.1007/s00424-006-0112-3) 17021801 · DOI
  38. [39]Lin YF, Jan YN, Jan LY 2000 Regulation of ATP-sensitive potassium channel function by protein kinase A-mediated phosphorylation in transfected HEK293 cells. EMBO J. 19, 942– 955. (10.1093/emboj/19.5.942) 10698936 PMC305634 · DOI
  39. [40]Hu K, Huang CS, Jan YN, Jan LY 2003 ATP-sensitive potassium channel traffic regulation by adenosine and protein kinase C. Neuron 38, 417– 432. (10.1016/S0896-6273(03)00256-3) 12741989 · DOI
  40. [41]Xie LH, Takano M, Kakei M, Okamura M, Noma A 1999 Wortmannin, an inhibitor of phosphatidylinositol kinases, blocks the MgATP-dependent recovery of Kir6.2/SUR2A channels. J. Physiol. 514(Pt 3), 655– 665. (10.1111/j.1469-7793.1999.655ad.x) 9882737 PMC2269097 · DOI
  41. [42]Furukawa T, Virag L, Furukawa N, Sawanobori T, Hiraoka M 1994 Mechanism for reactivation of the ATP-sensitive K+ channel by MgATP complexes in guinea-pig ventricular myocytes. J. Physiol. 479, 95– 107. (10.1113/jphysiol.1994.sp020280) 7990037 PMC1155728 · DOI
  42. [43]Kozlowski RZ, Ashford ML 1990 ATP-sensitive K+-channel run-down is Mg2+ dependent. Proc. R. Soc. Lond. B 240, 397– 410. (10.1098/rspb.1990.0044) 1974057 · DOI
  43. [44]Proks P, Takano M, Ashcroft FM 1994 Effects of intracellular pH on ATP-sensitive K+ channels in mouse pancreatic beta-cells. J. Physiol. 475, 33– 44. (10.1113/jphysiol.1994.sp020047) 8189391 PMC1160353 · DOI
  44. [45]Proks P, Ashcroft FM 1993 Modification of KATP channels in pancreatic beta-cells by trypsin. Pflugers Arch. 424, 63– 72. (10.1007/BF00375103) 8351206 · DOI
  45. [46]Furukawa T, Fan Z, Sawanobori T, Hiraoka M 1993 Modification of the adenosine 5'-triphosphate-sensitive K+ channel by trypsin in guinea-pig ventricular myocytes. J. Physiol. 466, 707– 726. (10.1113/jphysiol.1993.sp019741) 8410713 PMC1175499 · DOI
  46. [47]Nichols CG, Lopatin AN 1993 Trypsin and alpha-chymotrypsin treatment abolishes glibenclamide sensitivity of KATP channels in rat ventricular myocytes. Pflugers Arch. 422, 617– 619. (10.1007/BF00374011) 8469613 · DOI
  47. [48]Deutsch N, Weiss JN 1994 Effects of trypsin on cardiac ATP-sensitive K+ channels. Am. J. Physiol. 266, H613– H622. 8141363
  48. [49]Furukawa T, Yamane T, Terai T, Katayama Y, Hiraoka M 1996 Functional linkage of the cardiac ATP-sensitive K+ channel to the actin cytoskeleton. Pflugers Arch. 431, 504– 512. (10.1007/BF02191896) 8596692 · DOI
  49. [50]Tarasov AI, Girard CA, Ashcroft FM 2006 ATP sensitivity of the ATP-sensitive K+ channel in intact and permeabilized pancreatic beta-cells. Diabetes 55, 2446– 2454. (10.2337/db06-0360) 16936192 · DOI · Paper page
  50. [51]McKillen HC, Davies NW, Stanfield PR, Standen NB 1994 The effect of intracellular anions on ATP-dependent potassium channels of rat skeletal muscle. J. Physiol. 479, 341– 351. (10.1113/jphysiol.1994.sp020300) 7837093 PMC1155754 · DOI
  51. [53]Bokvist K, Ammala C, Ashcroft FM, Berggren PO, Larsson O, Rorsman P 1991 Separate processes mediate nucleotide-induced inhibition and stimulation of the ATP-regulated K+-channels in mouse pancreatic beta-cells. Proc. R. Soc. Lond. B 243, 139– 144. (10.1098/rspb.1991.0022) 1676517 · DOI · Paper page
  52. [54]Dawson RJ, Locher KP 2006 Structure of a bacterial multidrug ABC transporter. Nature 443, 180– 185. (10.1038/nature05155) 16943773 · DOI
  53. [55]Hohl M, Briand C, Grutter MG, Seeger MA 2012 Crystal structure of a heterodimeric ABC transporter in its inward-facing conformation. Nat. Struct. Mol. Biol. 19, 395– 402. (10.1038/nsmb.2267) 22447242 · DOI
  54. [56]Hohl M, Hurlimann LM, Bohm S, Schoppe J, Grutter MG, Bordignon E, Seeger MA 2014 Structural basis for allosteric cross-talk between the asymmetric nucleotide binding sites of a heterodimeric ABC exporter. Proc. Natl Acad. Sci. USA 111, 11 025– 11 030. (10.1073/pnas.1400485111) PMC4121816 25030449 · DOI
  55. [57]Li J, Jaimes KF, Aller SG 2014 Refined structures of mouse P-glycoprotein. Protein Sci. 23, 34– 46. (10.1002/pro.2387) 24155053 PMC3892297 · DOI
  56. [58]Locher KP 2009 Review. Structure and mechanism of ATP-binding cassette transporters. Phil. Trans. R. Soc. Lond. B 364, 239– 245. (10.1098/rstb.2008.0125) 18957379 PMC2674090 · DOI
  57. [59]Matsuo M, Tanabe K, Kioka N, Amachi T, Ueda K 2000 Different binding properties and affinities for ATP and ADP among sulfonylurea receptor subtypes, SUR1, SUR2A, and SUR2B. J. Biol. Chem. 275, 28 757– 28 763. (10.1074/jbc.M004818200) 10893240 · DOI
  58. [60]Matsuo M, Kimura Y, Ueda K 2005 KATP channel interaction with adenine nucleotides. J. Mol. Cell. Cardiol. 38, 907– 916. (10.1016/j.yjmcc.2004.11.021) 15910875 · DOI
  59. [61]Ueda K, Komine J, Matsuo M, Seino S, Amachi T 1999 Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide. Proc. Natl Acad. Sci. USA 96, 1268– 1272. (10.1073/pnas.96.4.1268) 9990013 PMC15452 · DOI
  60. [62]Tammaro P, Girard C, Molnes J, Njolstad PR, Ashcroft FM 2005 Kir6.2 mutations causing neonatal diabetes provide new insights into Kir6.2-SUR1 interactions. EMBO J. 24, 2318– 2330. (10.1038/sj.emboj.7600715) 15962003 PMC1173155 · DOI
  61. [63]Hosy E, Vivaudou M 2014 The unusual stoichiometry of ADP activation of the KATP channel. Front. Physiol. 5, 11 (10.3389/fphys.2014.00011) 24478723 PMC3904077 · DOI

Cited by

Sorted by citations

Authors
Proks, P., Puljung, M. C., Vedovato, N., Sachse, G., Mulvaney, R., & Ashcroft, F. M.
Affiliations
University of Oxford (GB)
Corresponding author
Ashcroft, Frances M.
ORCID
Venue
Philosophical Transactions of the Royal Society B: Biological Sciences
Publisher
The Royal Society
Published
2016-08-05
Volume
371
Issue
1700
Pages
20150426
ISSN
  • 0962-8436 (ISSN-L)
  • 1471-2970
DOI
10.1098/rstb.2015.0426
PMC
PMC4938026
OpenAlex
W2470292920
Cited by
11
References
2
Citations by year
2022: 1 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 1
FWCI
0.15
Type
journal article
Language
en
Update notices
correction (2016-09-05)
Open access
Licence
Locations
  • Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Oxford University Research Archive (ORA) (University of Oxford) (acceptedVersion, cc-by)
Funders
  • Wellcome Trust (046692)
  • Sixth Framework Programme (322620)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
ATP-sensitive potassium channels, rundown, nucleotide activation, Kir6.2, sulfonylurea receptor, phosphoinositides, channel regulation, excitable cells
MeSH terms
Animals, Biological Transport, Nucleotides, KATP Channels

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review