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(Received for publication, December 3, 1996, and in revised form, December 27, 1996)
From the Department of Medicine, University of Wisconsin, Madison,
Wisconsin 53792 and University of Chicago, Chicago, Illinois 60637
The ATP-sensitive potassium channel (KATP)
controls insulin release in pancreatic
Volume 272, Number 9,
Issue of February 28, 1997
pp. 5388-5395
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
-cells and also modulates
important functions in other cell types. In this study we report that
anionic phospholipids activated KATP in pancreatic -cells, cardiac
myocytes, skeletal muscle cells, and a cloned KATP composed of two
subunits (SUR/Kir6.2) stably expressed in a mammalian cell line. The
effectiveness was proportional to the number of negative charges on the
head group of the anionic phospholipid. Screening negative charges with
polyvalent cations antagonized the effect. Enzymatic treatment with
phospholipases that reduced charge on the lipids also reduced or
eliminated the effect. These results suggest that intact phospholipids
with negative charges are the critical requirement for activation of
KATP, in distinction from the usual cell signaling pathway through
phospholipids that requires cleavage. Mutations of two positively
charged amino acid residues at the C terminus of Kir6.2 accelerated
loss of channel activity and reduced the activating effects of
phospholipids, suggesting involvement of this region in the activation.
Metabolism of anionic phospholipids in plasmalemmal membrane may be a
novel and general mechanism for regulation of KATP and perhaps other ion channels in the family of inward rectifiers.
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W. A. Chutkow, J. C. Makielski, D. J. Nelson, C. F. Burant, and Z. Fan Alternative Splicing of sur2 Exon 17 Regulates Nucleotide Sensitivity of the ATP-sensitive Potassium Channel J. Biol. Chem., May 7, 1999; 274(19): 13656 - 13665. [Abstract] [Full Text] [PDF]
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A. B. Zhainazarov and B. W. Ache Effects of Phosphatidylinositol 4,5-Bisphosphate and Phosphatidylinositol 4-Phosphate on a Na+-Gated Nonselective Cation Channel J. Neurosci., April 15, 1999; 19(8): 2929 - 2937. [Abstract] [Full Text] [PDF]
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 L. Aguilar-Bryan and J. Bryan Molecular Biology of Adenosine Triphosphate-Sensitive Potassium Channels Endocr. Rev., April 1, 1999; 20(2): 101 - 135. [Abstract] [Full Text]
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 I. Heilmann, I. Y. Perera, W. Gross, and W. F. Boss Changes in Phosphoinositide Metabolism with Days in Culture Affect Signal Transduction Pathways in Galdieria sulphuraria Plant Physiology, April 1, 1999; 119(4): 1331 - 1340. [Abstract] [Full Text]
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I. H. M. Ho and R. D. Murrell-Lagnado Molecular Determinants for Sodium-dependent Activation of G Protein-gated K+ Channels J. Biol. Chem., March 26, 1999; 274(13): 8639 - 8648. [Abstract] [Full Text] [PDF]
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L.-H. Xie, M. Takano, M. Kakei, M. Okamura, and A. Noma Wortmannin, an inhibitor of phosphatidylinositol kinases, blocks the MgATP-dependent recovery of Kir6.2/SUR2A channels J. Physiol., February 1, 1999; 514(3): 655 - 665. [Abstract] [Full Text] [PDF]
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 Y Sai, A. Nies, and I. Arias Bile acid secretion and direct targeting of mdr1-green fluorescent protein from Golgi to the canalicular membrane in polarized WIF-B cells J. Cell Sci., January 12, 1999; 112(24): 4535 - 4545. [Abstract] [PDF]
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 S. Shyng and C. G. Nichols Membrane Phospholipid Control of Nucleotide Sensitivity of KATP Channels Science, November 6, 1998; 282(5391): 1138 - 1141. [Abstract] [Full Text]
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T. Baukrowitz, U. Schulte, D. Oliver, S. Herlitze, T. Krauter, S. J. Tucker, J. P. Ruppersberg, and B. Fakler PIP2 and PIP as Determinants for ATP Inhibition of KATP Channels Science, November 6, 1998; 282(5391): 1141 - 1144. [Abstract] [Full Text]
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F. M. Gribble, P. Proks, B. E. Corkey, and F. M. Ashcroft Mechanism of Cloned ATP-sensitive Potassium Channel Activation by Oleoyl-CoA J. Biol. Chem., October 9, 1998; 273(41): 26383 - 26387. [Abstract] [Full Text] [PDF]
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 G. G. MacGregor, J. Z. Xu, C. M. McNicholas, G. Giebisch, and S. C. Hebert Partially active channels produced by PKA site mutation of the cloned renal K+ channel, ROMK2 (kir1.2) Am J Physiol Renal Physiol, September 1, 1998; 275(3): F415 - F422. [Abstract] [Full Text] [PDF]
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X W Niu and R W Meech The effect of polyamines on KATP channels in guinea-pig ventricular myocytes J. Physiol., April 15, 1998; 508(2): 401 - 411. [Abstract] [Full Text] [PDF]
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S. Gudi, J. P. Nolan, and J. A. Frangos Modulation of GTPase activity of G proteins by fluid shear stress and phospholipid composition PNAS, March 3, 1998; 95(5): 2515 - 2519. [Abstract] [Full Text] [PDF]
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J. L. Sui, J. Petit-Jacques, and D. E. Logothetis Activation of the atrial KACh channel by the beta gamma subunits of G proteins or intracellular Na+ ions depends on the presence of phosphatidylinositol phosphates PNAS, February 3, 1998; 95(3): 1307 - 1312. [Abstract] [Full Text] [PDF]
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 L. AGUILAR-BRYAN, J. P. CLEMENT IV, G. GONZALEZ, K. KUNJILWAR, A. BABENKO, and J. BRYAN Toward Understanding the Assembly and Structure of KATP Channels Physiol Rev, January 1, 1998; 78(1): 227 - 245. [Abstract] [Full Text] [PDF]
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F. M. Gribble, G. Loussouarn, S. J. Tucker, C. Zhao, C. G. Nichols, and F. M. Ashcroft A Novel Method for Measurement of Submembrane ATP Concentration J. Biol. Chem., September 22, 2000; 275(39): 30046 - 30049. [Abstract] [Full Text] [PDF]
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H. Cho, G.-B. Nam, S. H. Lee, Y. E. Earm, and W.-K. Ho Phosphatidylinositol 4,5-Bisphosphate Is Acting as a Signal Molecule in alpha 1-Adrenergic Pathway via the Modulation of Acetylcholine-activated K+ Channels in Mouse Atrial Myocytes J. Biol. Chem., January 5, 2001; 276(1): 159 - 164. [Abstract] [Full Text] [PDF]
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H. Xu, N. Cui, Z. Yang, J. Wu, L. R. Giwa, L. Abdulkadir, P. Sharma, and C. Jiang Direct Activation of Cloned KATP Channels by Intracellular Acidosis J. Biol. Chem., April 13, 2001; 276(16): 12898 - 12902. [Abstract] [Full Text] [PDF]
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D.-K. Song and F. M. Ashcroft ATP Modulation of ATP-sensitive Potassium Channel ATP Sensitivity Varies with the Type of SUR Subunit J. Biol. Chem., March 2, 2001; 276(10): 7143 - 7149. [Abstract] [Full Text] [PDF]
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G. Loussouarn, L. J. Pike, F. M. Ashcroft, E. N. Makhina, and C. G. Nichols Dynamic Sensitivity of ATP-sensitive K+ Channels to ATP J. Biol. Chem., July 27, 2001; 276(31): 29098 - 29103. [Abstract] [Full Text] [PDF]
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