![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 63, Issue 3, 646-652, March 2003
Department of Physiology, Semmelweis University of Medicine,
Budapest, Hungary
TASK channels are highly pH-sensitive two-pore-domain background
potassium channels expressed in the central nervous system and in some
peripheral tissues. Their current can be regulated by receptor-mediated
activation of phospholipase C and also by pharmacological means. We
have reported previously that the cationic dye, ruthenium red (RR),
inhibited homodimeric TASK-3 (kcnk9), whereas TASK-1 (kcnk3) homodimer
and TASK-1/TASK-3 heterodimer were not affected by this compound. In
the present study, we identify the molecular determinant of the
RR-mediated TASK-3 inhibition. Mutation of the negatively charged Glu
70 of TASK-3 to Arg (E70R) or Cys (E70C) abolished the inhibitory
action of RR. When two TASK-3 coding sequences were concatenated, and
the entire homodimer was expressed as a single polypeptide chain, the
resulting tandem channel was also sensitive to RR. Mutation of Glu 70 in either the first (E70R) or the second (E465R) linked subunit
prevented the action of the inhibitor. Together with the Hill
coefficient of 1.0 for TASK-3 inhibition, these data indicate that
simultaneous binding of one polycationic RR molecule to Glu 70 of both
subunits is required for the inhibitory action. The pivotal role of
this residue in the inhibitory mechanism of RR is confirmed by the gained RR sensitivity of the mutant TASK-1 in which Lys 70 was changed
to Glu. Our results indicate that RR inhibits TASK-3 by tethering its
two subunits and identify amino acid 70 as a possible target for
designing selective inhibitors against the different TASK channels.
This article has been cited by other articles:
|
|
 |
|
  D. Kim, E. J. Cavanaugh, I. Kim, and J. L. Carroll Heteromeric TASK-1/TASK-3 is the major oxygen-sensitive background K+ channel in rat carotid body glomus cells J. Physiol., June 15, 2009; 587(12): 2963 - 2975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Clarke, E. L. Veale, K. Wyse, J. I. Vandenberg, and A. Mathie The M1P1 Loop of TASK3 K2P Channels Apposes the Selectivity Filter and Influences Channel Function J. Biol. Chem., June 20, 2008; 283(25): 16985 - 16992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Meuth, S. Bittner, P. Meuth, O. J. Simon, T. Budde, and H. Wiendl TWIK-related Acid-sensitive K+ Channel 1 (TASK1) and TASK3 Critically Influence T Lymphocyte Effector Functions J. Biol. Chem., May 23, 2008; 283(21): 14559 - 14570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Putzke, K. Wemhoner, F. B. Sachse, S. Rinne, G. Schlichthorl, X. T. Li, L. Jae, I. Eckhardt, E. Wischmeyer, H. Wulf, et al. The acid-sensitive potassium channel TASK-1 in rat cardiac muscle Cardiovasc Res, July 1, 2007; 75(1): 59 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zanzouri, I. Lauritzen, F. Duprat, M. Mazzuca, F. Lesage, M. Lazdunski, and A. Patel Membrane Potential-regulated Transcription of the Resting K+ Conductance TASK-3 via the Calcineurin Pathway J. Biol. Chem., September 29, 2006; 281(39): 28910 - 28918. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Musset, S. G. Meuth, G. X. Liu, C. Derst, S. Wegner, H.-C. Pape, T. Budde, R. Preisig-Muller, and J. Daut Effects of divalent cations and spermine on the K+ channel TASK-3 and on the outward current in thalamic neurons J. Physiol., May 1, 2006; 572(3): 639 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Meuth, M. I. Aller, T. Munsch, T. Schuhmacher, T. Seidenbecher, P. Meuth, C. Kleinschnitz, H.-C. Pape, H. Wiendl, W. Wisden, et al. The Contribution of TWIK-Related Acid-Sensitive K+-Containing Channels to the Function of Dorsal Lateral Geniculate Thalamocortical Relay Neurons Mol. Pharmacol., April 1, 2006; 69(4): 1468 - 1476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Czirjak and P. Enyedi Zinc and Mercuric Ions Distinguish TRESK from the Other Two-Pore-Domain K+ Channels Mol. Pharmacol., March 1, 2006; 69(3): 1024 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I. Aller, E. L. Veale, A.-M. Linden, C. Sandu, M. Schwaninger, L. J. Evans, E. R. Korpi, A. Mathie, W. Wisden, and S. G. Brickley Modifying the Subunit Composition of TASK Channels Alters the Modulation of a Leak Conductance in Cerebellar Granule Neurons J. Neurosci., December 7, 2005; 25(49): 11455 - 11467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Kim, J.-Y. Park, H.-W. Kang, E.-J. Lee, H. Bang, and J.-H. Lee Zinc Activates TREK-2 Potassium Channel Activity J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 618 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. El Kouhen, C. S. Surowy, B. R. Bianchi, T. R. Neelands, H. A. McDonald, W. Niforatos, A. Gomtsyan, C.-H. Lee, P. Honore, J. P. Sullivan, et al. A-425619 [1-Isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a Novel and Selective Transient Receptor Potential Type V1 Receptor Antagonist, Blocks Channel Activation by Vanilloids, Heat, and Acid J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 400 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E Clarke, E. L Veale, P. J Green, H. J Meadows, and A. Mathie Selective block of the human 2-P domain potassium channel, TASK-3, and the native leak potassium current, IKSO, by zinc J. Physiol., October 1, 2004; 560(1): 51 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gruss, A. Mathie, W. R. Lieb, and N. P. Franks The Two-Pore-Domain K+ Channels TREK-1 and TASK-3 Are Differentially Modulated by Copper and Zinc Mol. Pharmacol., September 1, 2004; 66(3): 530 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. M. Choisy, J. C. Hancox, L. A. Arberry, A. M. Reynolds, M. J. Shattock, and A. F. James Evidence for a Novel K+ Channel Modulated by {alpha}1A-Adrenoceptors in Cardiac Myocytes Mol. Pharmacol., September 1, 2004; 66(3): 735 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Berg, E. M. Talley, J. P. Manger, and D. A. Bayliss Motoneurons Express Heteromeric TWIK-Related Acid-Sensitive K+ (TASK) Channels Containing TASK-1 (KCNK3) and TASK-3 (KCNK9) Subunits J. Neurosci., July 28, 2004; 24(30): 6693 - 6702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kang, J. Han, E. M. Talley, D. A. Bayliss, and D. Kim Functional expression of TASK-1/TASK-3 heteromers in cerebellar granule cells J. Physiol., January 1, 2004; 554(1): 64 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Lauritzen, M. Zanzouri, E. Honore, F. Duprat, M. U. Ehrengruber, M. Lazdunski, and A. J. Patel K+-dependent Cerebellar Granule Neuron Apoptosis: ROLE OF TASK LEAK K+ CHANNELS J. Biol. Chem., August 22, 2003; 278(34): 32068 - 32076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wrayzx, K. Jones, S. Kupittayanant, Y. Li, A. Matthew, E. Monir-Bishty, K. Noble, S. J. Pierce, S. Quenby, and A. V. Shmygol Calcium Signaling and Uterine Contractility Reproductive Sciences, July 1, 2003; 10(5): 252 - 264. [Abstract] [PDF]
|
|
|
|
 |
|
 D. A. Bayliss, J. E. Sirois, and E. M. Talley The TASK Family: Two-Pore Domain Background K+ Channels Mol. Interv., June 1, 2003; 3(4): 205 - 219. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
