| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Molecular and Genomic |
1 Institut für Physiologie, Universität Marburg, Deutschhausstrasse 2, 35037 Marburg, Germany
2 Klinik für Neurologie, Universität Würzburg, 97080 Würzburg, Germany
3 Institut für Physiologie I, Universität Münster, 48149 Münster, Germany
4 Institut für Experimentelle Epilepsieforschung, Universität Münster, 48149 Münster, Germany
The potassium channels TASK-1 and TASK-3 show high sequence homology but differ in their sensitivity to extracellular divalent cations. Heterologous expression in HEK293 cells showed that the single-channel conductance of TASK-3 increased approximately four-fold after removal of external divalent cations, whereas the conductance of TASK-1 was unaffected. Replacing the glutamate at position 70 of TASK-3 by a lysine or arginine residue abolished the sensitivity to divalent cations. The reverse mutation in TASK-1 (K70E) induced sensitivity to divalent cations. The organic polycations spermine and ruthenium red modulated the conductance of TASK-3 in a similar way as Ca2+ or Mg2+. Our data suggest that these effects were mediated by shielding of the negative charges in the extracellular loops of TASK-3. Whole-cell currents carried by TASK-3 channels were inhibited by spermine and ruthenium red even in the presence of external divalent cations. These data suggest that, in addition to their effect on single-channel conductance, spermine and ruthenium red decreased the open probability of TASK-3 channels, probably by binding to residue E70. The standing outward current in thalamocortical relay neurons, which is largely carried by TASK channels, was also inhibited by divalent cations and spermine. Using the differential sensitivity of TASK-1 and TASK-3 to divalent cations and spermine we found that about 20% of the standing outward current in thalamocortical relay neurons flows through TASK-3 channels. We conclude from our results that inhibition of TASK-3 channels may contribute to the neuromodulatory effect of spermine released from neurons during repetitive activity or during hypoxia.
(Received 3 February 2006;
accepted after revision 27 February 2006;
first published online 2 March 2006)
Corresponding author J. Daut: Institut für Physiologie der Universität Marburg, Deutschhausstrasse 2, 35037 Marburg, Germany. Email: jdaut{at}staff.uni-marburg.de
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
 |
|
 S. G. Meuth, T. Kanyshkova, P. Meuth, P. Landgraf, T. Munsch, A. Ludwig, F. Hofmann, H.-C. Pape, and T. Budde Membrane Resting Potential of Thalamocortical Relay Neurons Is Shaped by the Interaction Among TASK3 and HCN2 Channels J Neurophysiol, September 1, 2006; 96(3): 1517 - 1529. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
