© 2000 American Heart Association, Inc.
Cellular Biology |
Effects of the Renin-Angiotensin System on the Current Ito in Epicardial and Endocardial Ventricular Myocytes From the Canine Heart
From the Departments of Physiology and Biophysics (H.Y., J.G., H.W., I.S.C.) and Neurobiology and Behavior (D.M.) and Institute of Molecular Cardiology (H.Y., J.G., H.W., R.W., D.M., M.R.R., I.S.C.), State University of New York at Stony Brook; Department of Pharmacology, Pediatrics and Medicine (S.S., M.R.R.), Columbia University, College of Physicians and Surgeons, New York, NY; and Department of Biological Science (R.W.), University of Tulsa, Tulsa, Okla.
Correspondence to Dr Ira S. Cohen, Institute of Molecular Cardiology, 8661 SUNY, Stony Brook, NY 11794-8661. E-mail icohen{at}physiology.pnb.sunysb.edu
Abstract—The
Ca2+-independent portion of transient outward
K+ current (Ito) exhibits a
transmural gradient in ventricle. To investigate control mechanisms for
this gradient, we studied canine epicardial and endocardial
ventricular myocytes with use of the whole-cell patch-clamp
technique. Ito was larger in amplitude, had
a more negative voltage threshold for activation, and had a more
negative midpoint of inactivation in epicardium. Recovery from
inactivation was >10-fold slower in endocardium. Incubation of
epicardial myocytes with angiotensin II for 2 to 52 hours
altered Ito to resemble unincubated
endocardium and reduced the amplitude of the phase 1 notch of the
action potential. In contrast, incubation of endocardial myocytes with
losartan for 2 to 52 hours altered
Ito to resemble unincubated epicardium and
induced a phase 1 notch in the action potential. With RNase protection
assays, we determined that incubations with angiotensin II
or losartan did not alter mRNA levels for either Kv4.3 or
Kv1.4; thus, a change in the 
subunit for
Ito is unlikely to be responsible. To test
whether posttranslational modification produced the effects of
angiotensin II, we coexpressed Kv4.3 and the
angiotensin II type 1a receptor in Xenopus
oocytes. Incubation with angiotensin II increased the time
constant for recovery from inactivation of the expressed current by
2-fold with an incubation time constant of 3.7 hours. No effect on
activation or inactivation voltage dependence was observed. These
results demonstrate that the properties of
Ito in endocardium and epicardium are
plastic and likely under the tonic-differing influence of the
renin-angiotensin system.
Key Words: angiotensin • epicardium • endocardium • current
This article has been cited by other articles:
 |
|
 |
|
  K. Rivard, P. Paradis, M. Nemer, and C. Fiset Cardiac-specific overexpression of the human type 1 angiotensin II receptor causes delayed repolarization Cardiovasc Res, April 1, 2008; 78(1): 53 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Goette and U. Lendeckel Electrophysiological effects of angiotensin II. Part I: signal transduction and basic electrophysiological mechanisms Europace, February 1, 2008; 10(2): 238 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. S. Kasi, H. D. Xiao, L. L. Shang, S. Iravanian, J. Langberg, E. A. Witham, Z. Jiao, C. J. Gallego, K. E. Bernstein, and S. C. Dudley Jr. Cardiac-restricted angiotensin-converting enzyme overexpression causes conduction defects and connexin dysregulation Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H182 - H192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Saygili, O. R. Rana, E. Saygili, H. Reuter, K. Frank, R. H. G. Schwinger, J. Muller-Ehmsen, and C. Zobel Losartan prevents stretch-induced electrical remodeling in cultured atrial neonatal myocytes Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2898 - H2905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Fiset and W. R. Giles Transmural Gradients of Repolarization and Excitation-Contraction Coupling in Mouse Ventricle Circ. Res., May 26, 2006; 98(10): 1237 - 1239. [Full Text] [PDF]
|
|
|
|
|
|
Y. Shimoni, D. Hunt, K. Chen, T. Emmett, and G. Kargacin Differential autocrine modulation of atrial and ventricular potassium currents and of oxidative stress in diabetic rats Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1879 - H1888. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Rosen and I. S. Cohen Cardiac memory ... new insights into molecular mechanisms J. Physiol., January 15, 2006; 570(2): 209 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gao, W. Wang, I. S. Cohen, and R. T. Mathias Transmural Gradients in Na/K Pump Activity and [Na+]i in Canine Ventricle Biophys. J., September 1, 2005; 89(3): 1700 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Sun and H.-S. Wang Role of the transient outward current (Ito) in shaping canine ventricular action potential - a dynamic clamp study J. Physiol., April 15, 2005; 564(2): 411 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Szentadrassy, T. Banyasz, T. Biro, G. Szabo, B. I. Toth, J. Magyar, J. Lazar, A. Varro, L. Kovacs, and P. P. Nanasi Apico-basal inhomogeneity in distribution of ion channels in canine and human ventricular myocardium Cardiovasc Res, March 1, 2005; 65(4): 851 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. Doronin, I. A. Potapova, Z. Lu, and I. S. Cohen Angiotensin Receptor Type 1 Forms a Complex with the Transient Outward Potassium Channel Kv4.3 and Regulates Its Gating Properties and Intracellular Localization J. Biol. Chem., November 12, 2004; 279(46): 48231 - 48237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. F. Tomaselli and D. P. Zipes What Causes Sudden Death in Heart Failure? Circ. Res., October 15, 2004; 95(8): 754 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Dun, S. Baba, T. Yagi, and P. A. Boyden Dynamic remodeling of K+ and Ca2+ currents in cells that survived in the epicardial border zone of canine healed infarcted heart Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1046 - H1054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Potapova, A. Plotnikov, Z. Lu, P. Danilo Jr, V. Valiunas, J. Qu, S. Doronin, J. Zuckerman, I. N. Shlapakova, J. Gao, et al. Human Mesenchymal Stem Cells as a Gene Delivery System to Create Cardiac Pacemakers Circ. Res., April 16, 2004; 94(7): 952 - 959. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Cerbai and A. Mugelli Angiotensin AT2 receptor: the younger sibling attracts attention Cardiovasc Res, April 1, 2004; 62(1): 7 - 8. [Full Text] [PDF]
|
|
|
|
|
|
R. Caballero, R. Gomez, I. Moreno, L. Nunez, T. Gonzalez, C. Arias, M. Guizy, C. Valenzuela, J. Tamargo, and E. Delpon Interaction of angiotensin II with the angiotensin type 2 receptor inhibits the cardiac transient outward potassium current Cardiovasc Res, April 1, 2004; 62(1): 86 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Valiunas, S. Doronin, L. Valiuniene, I. Potapova, J. Zuckerman, B. Walcott, R. B. Robinson, M. R. Rosen, P. R. Brink, and I. S. Cohen Human mesenchymal stem cells make cardiac connexins and form functional gap junctions J. Physiol., March 15, 2004; 555(3): 617 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shimoni, M. Chuang, E. D. Abel, and David. L. Severson Gender-dependent attenuation of cardiac potassium currents in type 2 diabetic db/db mice J. Physiol., March 1, 2004; 555(2): 345 - 354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Rosen, O. Binah, and S. Marom Cardiac Memory and Cortical Memory: Do Learning Patterns in Neural Networks Impact on Cardiac Arrhythmias? Circulation, October 14, 2003; 108(15): 1784 - 1789. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Patberg, A. N. Plotnikov, A. Quamina, R. Z. Gainullin, A. Rybin, P. Danilo Jr, L. S. Sun, and M. R. Rosen Cardiac Memory Is Associated With Decreased Levels of the Transcriptional Factor CREB Modulated by Angiotensin II and Calcium Circ. Res., September 5, 2003; 93(5): 472 - 478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Plotnikov, H. Yu, J. C. Geller, R. Z. Gainullin, P. Chandra, K. W. Patberg, S. Friezema, P. Danilo Jr, I. S. Cohen, S. J. Feinmark, et al. Role of L-Type Calcium Channels in Pacing-Induced Short-Term and Long-Term Cardiac Memory in Canine Heart Circulation, June 10, 2003; 107(22): 2844 - 2849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Rosen The Electrocardiogram 100 Years Later: Electrical Insights Into Molecular Messages Circulation, October 22, 2002; 106(17): 2173 - 2179. [Full Text] [PDF]
|
|
|
|
|
|
Members of the Sicilian Gambit New Approaches to Antiarrhythmic Therapy, Part II: Emerging Therapeutic Applications of the Cell Biology of Cardiac Arrhythmias Circulation, December 11, 2001; 104(24): 2990 - 2994. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Members of the Sicilian Gambit New Approaches to Antiarrhythmic Therapy, Part I: Emerging Therapeutic Applications of the Cell Biology of Cardiac Arrhythmias Circulation, December 4, 2001; 104(23): 2865 - 2873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Members of the Sicilian Gambit New approaches to antiarrhythmic therapy; emerging therapeutic applications of the cell biology of cardiac arrhythmias Eur. Heart J., December 1, 2001; 22(23): 2148 - 2163. [Abstract] [PDF]
|
|
|
|
|
|
Members of the Sicilian Gambit New approaches to antiarrhythmic therapy: emerging therapeutic applications of the cell biology of cardiac arrhythmias Cardiovasc Res, December 1, 2001; 52(3): 345 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nabauer Tuning Repolarization in the Heart : A Multitude of Potassium Channels and Regulatory Pathways Circ. Res., March 16, 2001; 88(5): 453 - 455. [Full Text] [PDF]
|
|
|
|
|
|
J. L. Greenstein, R. Wu, S. Po, G. F. Tomaselli, and R. L. Winslow Role of the Calcium-Independent Transient Outward Current Ito1 in Shaping Action Potential Morphology and Duration Circ. Res., November 24, 2000; 87(11): 1026 - 1033. [Abstract] [Full Text] [PDF]
|
|