| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Physiologisches Institut, 8057 Zürich, Switzerland; and 2 Institut de Pharmacologie du Centre National de la Recherche Scientifique, 06560 Valbonne Sophia-Antipolis, France
Mutations of the KCNE1 gene (IsK, minK) are related to hereditary forms of cardiac arrhythmias, so-called long QT syndromes (LQT). Here we review the phenotype of a mouse model for the recessive form of LQT known as Jervell and Lange-Nielsen syndrome. KCNE1 knockout mice exhibit an enhanced QT-RR adaptability, which is probably part of the pathophysiological mechanism leading to life-threatening tachyarrhythmia in patients. Like patients, knockout mice are deaf and show vestibular symptoms due to an impaired endolymph production. Knockout mice show urinary and fecal salt wasting and volume depletion. The renal phenotype is due to diminished reabsorption of Na+ and glucose. The mice are hypokalemic and have increased aldosterone levels. Besides volume depletion, aldosterone is elevated via a set-point shift for sensing of extracellular K+ in aldosterone-secreting glomerulosa cells, which physiologically express KCNE1. In conclusion, KCNE1 knockout leads to a complex phenotype resulting from direct loss of KCNE1 and compensatory mechanisms. Murine KCNE1 physiology could be helpful for the pathophysiological understanding and perhaps gene-specific treatment of long QT patients.
KvLQT1; long QT syndrome; kidney; heart
This article has been cited by other articles:
|
|
 |
|
  D. Heitzmann and R. Warth Physiology and Pathophysiology of Potassium Channels in Gastrointestinal Epithelia Physiol Rev, July 1, 2008; 88(3): 1119 - 1182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Heitzmann and R. Warth No Potassium, No Acid: K+ Channels and Gastric Acid Secretion Physiology, October 1, 2007; 22(5): 335 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Eugene, S. Deforges, F. Guimont, E. Idoux, P.-P. Vidal, L. E. Moore, and N. Vibert Developmental regulation of the membrane properties of central vestibular neurons by sensory vestibular information in the mouse J. Physiol., September 15, 2007; 583(3): 923 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Panaghie and G. W. Abbott The Role of S4 Charges in Voltage-dependent and Voltage-independent KCNQ1 Potassium Channel Complexes J. Gen. Physiol., January 29, 2007; 129(2): 121 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Thomas, M. J. Killeen, I. S. Gurung, P. Hakim, R. Balasubramaniam, C. A. Goddard, A. A. Grace, and C. L.-H. Huang Mechanisms of ventricular arrhythmogenesis in mice following targeted disruption of KCNE1 modelling long QT syndrome 5 J. Physiol., January 1, 2007; 578(1): 99 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Willems, M. E. Reichelt, J. G. Molina, C.-X. Sun, J. L. Chunn, K. J. Ashton, J. Schnermann, M. R. Blackburn, and J. P. Headrick Effects of adenosine deaminase and A1 receptor deficiency in normoxic and ischaemic mouse hearts Cardiovasc Res, July 1, 2006; 71(1): 79 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Jespersen, M. Grunnet, and S.-P. Olesen The KCNQ1 Potassium Channel: From Gene to Physiological Function Physiology, December 1, 2005; 20(6): 408 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Milan and C. A. MacRae Animal models for arrhythmias Cardiovasc Res, August 15, 2005; 67(3): 426 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Reichelt, L. Willems, J. G. Molina, C.-X. Sun, J. C. Noble, K. J. Ashton, J. Schnermann, M. R. Blackburn, and J. P. Headrick Genetic Deletion of the A1 Adenosine Receptor Limits Myocardial Ischemic Tolerance Circ. Res., February 18, 2005; 96(3): 363 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Hebert, G. Desir, G. Giebisch, and W. Wang Molecular Diversity and Regulation of Renal Potassium Channels Physiol Rev, January 1, 2005; 85(1): 319 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Heitzmann, F. Grahammer, T. von Hahn, A. Schmitt-Graff, E. Romeo, R. Nitschke, U. Gerlach, H. J. Lang, F. Verrey, J. Barhanin, et al. Heteromeric KCNE2/KCNQ1 potassium channels in the luminal membrane of gastric parietal cells J. Physiol., December 1, 2004; 561(2): 547 - 557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Jespersen, H. B. Rasmussen, M. Grunnet, H. S. Jensen, K. Angelo, D. S. Dupuis, L. K. Vogel, N. K. Jorgensen, D. A. Klaerke, and S.-P. Olesen Basolateral localisation of KCNQ1 potassium channels in MDCK cells: molecular identification of an N-terminal targeting motif J. Cell Sci., September 1, 2004; 117(19): 4517 - 4526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-P. Vidal, L. Degallaix, P. Josset, J.-P. Gasc, and K. E. Cullen Postural and locomotor control in normal and vestibularly deficient mice J. Physiol., September 1, 2004; 559(2): 625 - 638. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Priori Inherited Arrhythmogenic Diseases: The Complexity Beyond Monogenic Disorders Circ. Res., February 6, 2004; 94(2): 140 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Balasubramaniam, A. A Grace, R. C Saumarez, J. I Vandenberg, and C. L-H Huang Electrogram prolongation and nifedipine-suppressible ventricular arrhythmias in mice following targeted disruption of KCNE1 J. Physiol., October 15, 2003; 552(2): 535 - 546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Grunnet, T. Jespersen, N. MacAulay, N. K Jorgensen, N. Schmitt, O. Pongs, S.-P. Olesen, and D. A Klaerke KCNQ1 channels sense small changes in cell volume J. Physiol., June 1, 2003; 549(2): 419 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ehmke Mouse gene targeting in cardiovascular physiology Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2003; 284(1): R28 - R30. [Full Text] [PDF]
|
|
|
|
|
|
H. Ehmke Physiological functions of the regulatory potassium channel subunit KCNE1 Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2002; 282(3): R637 - R638. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
