| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Physiology, Centre Medical Universitaire Geneva, Geneva, Geneva, Switzerland
2 Sanofi-Synthelabo, Rueil Malmaison, France
3 Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom
* To whom correspondence should be addressed. E-mail: alex.baertschi{at}medecine.unige.ch.
Cardiomyocytes express mRNA for all major subunits of ATP-sensitive potassium channels (KATP): KIR6.1, KIR6.2, SUR1A, SUR2A, and SUR2B. It has remained controversial whether KIR6.1 may associate with KIR6.2 to form the tetrameric pore of KATP channels in cardiomyocytes. To explore this possibility, cultured rat cardiomyocytes were examined for an inhibition of the KATP current by over-expression of pore-loop mutated (inactive) KIR6.x. Bicistronic plasmids were constructed encoding loop mutated (AFA or SFG for GFG) rat KIR6.x followed by EGFP. In ventricular myocytes, the overexpression of KIR6.1SFG-pIRES2-EGFP or KIR6.2AFA-pIRES2-EGFP DNA caused after 72h a major decrease of the KATP current density of 85.8% and 82.7%, respectively (p<0.01), relative to EGFP controls (59±9pA/pF). In atrial myocytes, overexpression of these pore-mutated KIR6.x by 6.0-fold and 10.6-fold, as assessed by quantitative immunohistochemistry, caused a decrease of the KATP current density of 73.7% and 58.5%, respectively (p<0.01). Expression of wild type rat KIR6.2 increased the ventricular and atrial KATP current density by 58.3% and 42.9%, respectively (p<0.01), relative to corresponding EGFP controls, indicating a reserve of SUR to accommodate increased KIR6.x trafficking to the sarcolemma. The results favor the view that KIR6.1 may associate with KIR6.2 to form heterotetrameric pores of native KATP channels in cardiomyocytes.
This article has been cited by other articles:
|
|
 |
|
  P. Philip-Couderc, N. I. Tavares, A. Roatti, R. Lerch, C. Montessuit, and A. J. Baertschi Forkhead Transcription Factors Coordinate Expression of Myocardial KATP Channel Subunits and Energy Metabolism Circ. Res., February 1, 2008; 102(2): e20 - e35. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. W. Chan, A. Wheeler, and L. Csanady Sulfonylurea Receptors Type 1 and 2A Randomly Assemble to Form Heteromeric KATP Channels of Mixed Subunit Composition J. Gen. Physiol., December 31, 2007; 131(1): 43 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Tong, L. M. Porter, G. Liu, P. Dhar-Chowdhury, S. Srivastava, D. J. Pountney, H. Yoshida, M. Artman, G. I. Fishman, C. Yu, et al. Consequences of cardiac myocyte-specific ablation of KATP channels in transgenic mice expressing dominant negative Kir6 subunits Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H543 - H551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zhou, O. Tanaka, M. Sekiguchi, H.-j. He, Y. Yasuoka, H. Itoh, K. Kawahara, and H. Abe ATP-sensitive K+-channel Subunits on the Mitochondria and Endoplasmic Reticulum of Rat Cardiomyocytes J. Histochem. Cytochem., December 1, 2005; 53(12): 1491 - 1500. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
