© 2000 American Heart Association, Inc.
MiniReview |
Connexin Expression and Turnover
Implications for Cardiac Excitability
From the Departments of Pathology and Medicine and the Center for Cardiovascular Research, Washington University, St. Louis, Mo.
Correspondence to Jeffrey E. Saffitz, Department of Pathology, Box 8118, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110. E-mail saffitz{at}pathbox.wustl.edu
Abstract—Electrical activation of
the heart requires current transfer from one cell to another via gap
junctions, arrays of densely packed intercellular channels. The extent
to which cardiac myocytes are coupled is determined by multiple
mechanisms, including tissue-specific patterns of expression of diverse
gap junction channel proteins (connexins), and regulatory pathways that
control connexin synthesis, intracellular trafficking, assembly into
channels, and degradation. Many connexins, including those expressed in
the heart, have been found to turn over rapidly. Recent studies in the
intact adult heart suggest that connexin43, the principal cardiac
connexin, is surprisingly short-lived (half-life 
1.3 hours). Both
the proteasome and the lysosome participate in connexin43
degradation. Other ion channel proteins, such as those forming selected
voltage-gated K+ channels, may also exhibit rapid turnover
kinetics. Regulation of connexin degradation may be an important
mechanism for adjusting intercellular coupling in the heart under
normal and pathophysiological conditions.
Key Words: gap junctions • connexins • proteolysis • proteasome • lysosome
This article has been cited by other articles:
 |
|
 |
|
  A. C.G. van Ginneken MinK: a double-hearted partner in cardiac repolarization Cardiovasc Res, June 1, 2009; 82(3): 390 - 391. [Full Text] [PDF]
|
|
|
|
 |
|
 P. T. Ohara, J.-P. Vit, A. Bhargava, and L. Jasmin Evidence for a Role of Connexin 43 in Trigeminal Pain Using RNA Interference In Vivo J Neurophysiol, December 1, 2008; 100(6): 3064 - 3073. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Lisewski, Y. Shi, U. Wrackmeyer, R. Fischer, C. Chen, A. Schirdewan, R. Juttner, F. Rathjen, W. Poller, M. H. Radke, et al. The tight junction protein CAR regulates cardiac conduction and cell-cell communication J. Exp. Med., September 29, 2008; 205(10): 2369 - 2379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Yang, Y. Lu, and Z. Wang Control of cardiac excitability by microRNAs Cardiovasc Res, September 1, 2008; 79(4): 571 - 580. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sato, T. Ohkusa, H. Honjo, S. Suzuki, M.-a. Yoshida, Y. S. Ishiguro, H. Nakagawa, M. Yamazaki, M. Yano, I. Kodama, et al. Altered expression of connexin43 contributes to the arrhythmogenic substrate during the development of heart failure in cardiomyopathic hamster Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1164 - H1173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ruiz-Meana, A. Rodriguez-Sinovas, A. Cabestrero, K. Boengler, G. Heusch, and D. Garcia-Dorado Mitochondrial connexin43 as a new player in the pathophysiology of myocardial ischaemia-reperfusion injury Cardiovasc Res, January 15, 2008; 77(2): 325 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Matsushita, H. Kurihara, M. Watanabe, T. Okada, T. Sakai, and A. Amano Alterations of Phosphorylation State of Connexin 43 during Hypoxia and Reoxygenation Are Associated with Cardiac Function J. Histochem. Cytochem., March 1, 2006; 54(3): 343 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Li, V. V. Patel, and G. L. Radice Dysregulation of cell adhesion proteins and cardiac arrhythmogenesis. Clin. Med. Res., March 1, 2006; 4(1): 42 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Somekawa, S. Fukuhara, Y. Nakaoka, H. Fujita, Y. Saito, and N. Mochizuki Enhanced Functional Gap Junction Neoformation by Protein Kinase A-Dependent and Epac-Dependent Signals Downstream of cAMP in Cardiac Myocytes Circ. Res., September 30, 2005; 97(7): 655 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-L. Hao, K. Suzuki, Y. Lu, S. Hirano, K. Fukuda, N. Kumagai, K. Kimura, and T. Nishida Inhibition of Gap Junction-Mediated Intercellular Communication by TNF-{alpha} in Cultured Human Corneal Fibroblasts Invest. Ophthalmol. Vis. Sci., April 1, 2005; 46(4): 1195 - 1200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D. Spragg and D. A. Kass Controlling the Gap: Myocytes, Matrix, and Mechanics Circ. Res., March 18, 2005; 96(5): 485 - 487. [Full Text] [PDF]
|
|
|
|
 |
|
 U Wetzel, A Boldt, J Lauschke, J Weigl, P Schirdewahn, A Dorszewski, N Doll, G Hindricks, S Dhein, and H Kottkamp Expression of connexins 40 and 43 in human left atrium in atrial fibrillation of different aetiologies Heart, February 1, 2005; 91(2): 166 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Pollard, W. M. Smith, and R. C. Barr Feasibility of cardiac microimpedance measurement using multisite interstitial stimulation Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2402 - H2411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. G. Akar, D. D. Spragg, R. S. Tunin, D. A. Kass, and G. F. Tomaselli Mechanisms Underlying Conduction Slowing and Arrhythmogenesis in Nonischemic Dilated Cardiomyopathy Circ. Res., October 1, 2004; 95(7): 717 - 725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Turner, G. A. Haywood, P. Andreka, L. You, P. E. Martin, W. H. Evans, K. A. Webster, and N. H. Bishopric Reversible Connexin 43 Dephosphorylation During Hypoxia and Reoxygenation Is Linked to Cellular ATP Levels Circ. Res., October 1, 2004; 95(7): 726 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Maass, A. Ghanem, J.-S. Kim, M. Saathoff, S. Urschel, G. Kirfel, R. Grummer, M. Kretz, T. Lewalter, K. Tiemann, et al. Defective Epidermal Barrier in Neonatal Mice Lacking the C-Terminal Region of Connexin43 Mol. Biol. Cell, October 1, 2004; 15(10): 4597 - 4608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Inoue, T. Ohkusa, T. Nao, J.-K. Lee, T. Matsumoto, Y. Hisamatsu, T. Satoh, M. Yano, K. Yasui, I. Kodama, et al. Rapid electrical stimulation of contraction modulates gap junction protein in neonatal rat cultured cardiomyocytes: Involvement of mitogen-activated protein kinases and effects of angiotensin ii-receptor antagonist J. Am. Coll. Cardiol., August 18, 2004; 44(4): 914 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Nicholson Gap junctions - from cell to molecule J. Cell Sci., November 15, 2003; 116(22): 4479 - 4481. [Full Text] [PDF]
|
|
|
|
|
|
A. Hoffmann, T. Gloe, U. Pohl, and S. Zahler Nitric oxide enhances de novo formation of endothelial gap junctions Cardiovasc Res, November 1, 2003; 60(2): 421 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Eugenin, M. C. Branes, J. W. Berman, and J. C. Saez TNF-{alpha} Plus IFN-{gamma} Induce Connexin43 Expression and Formation of Gap Junctions Between Human Monocytes/Macrophages That Enhance Physiological Responses J. Immunol., February 1, 2003; 170(3): 1320 - 1328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Koval Sharing signals: connecting lung epithelial cells with gap junction channels Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L875 - L893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Kehat, A. Gepstein, A. Spira, J. Itskovitz-Eldor, and L. Gepstein High-Resolution Electrophysiological Assessment of Human Embryonic Stem Cell-Derived Cardiomyocytes: A Novel In Vitro Model for the Study of Conduction Circ. Res., October 18, 2002; 91(8): 659 - 661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Oahara, Y. Miyauchi, T. Ohara, M. C. Fishbein, S. Zhou, M.-H. Lee, W. J. Mandel, P.-S. Chen, and H. S. Karagueuzian Downregulation of Immunodetectable Atrial Connexin4O in a Canine Model of Chronic Left Ventricular Myocardial Infarction: Implications to Atrial Fibrillation Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2002; 7(2): 89 - 94. [Abstract] [PDF]
|
|
|
|
|
|
H. M.W van der Velden and H. J Jongsma Cardiac gap junctions and connexins: their role in atrial fibrillation and potential as therapeutic targets Cardiovasc Res, May 1, 2002; 54(2): 270 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. G. Akar, B. J. Roth, and D. S. Rosenbaum Optical measurement of cell-to-cell coupling in intact heart using subthreshold electrical stimulation Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H533 - H542. [Abstract] [Full Text] [PDF]
|
|