Published online before print March 28, 2002, doi: 10.1161/01.RES.0000016960.61087.86
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 7, 2002
Revised on March 15, 2002
Accepted on March 20, 2002
Ionic Current Basis of Electrocardiographic Waveforms. A Model Study
Kazutaka Gima and Yoram Rudy *
From the Cardiac Bioelectricity Research and Training Center, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.
* To whom correspondence should be addressed. E-mail: yxr{at}po.cwru.edu.
Body surface electrocardiograms and electrograms recorded from the surfaces of the heart are the basis for diagnosis and treatment of cardiac electrophysiological disorders and arrhythmias. Given recent advances in understanding the molecular mechanisms of arrhythmia, it is important to relate these electrocardiographic waveforms to cellular electrophysiological processes. This modeling study establishes the following principles: (1) voltage gradients created by heterogeneities of the slow-delayed rectifier (IKs) and transient outward (Ito) potassium current inscribe the T wave and J wave, respectively; T-wave polarity and width are strongly influenced by the degree of intercellular coupling through gap-junctions. (2) Changes in [K+]o modulate the T wave through their effect on the rapid-delayed rectifier, IKr. (3) Alterations of IKs, IKr, and INa (fast sodium current) in long-QT syndrome (LQT1, LQT2, and LQT3, respectively) are reflected in characteristic QT-interval and T-wave changes; LQT1 prolongs QT without widening the T wave. (4) Accelerated inactivation of INa on the background of large epicardial Ito results in ST elevation (Brugada phenotype) that reflects the degree of severity. (5) Activation of the ATP-sensitive potassium current, IK(ATP), is sufficient to cause ST elevation during acute ischemia. These principles provide a mechanistic cellular basis for interpretation of electrocardiographic waveforms.
Key words: electrocardiography • mathematical modeling • long-QT syndrome • Brugada syndrome • ischemia
This article has been cited by other articles:
 |
|
 |
|
  S. M. Narayan, J. D. Bayer, G. Lalani, and N. A. Trayanova Action Potential Dynamics Explain Arrhythmic Vulnerability in Human Heart Failure A Clinical and Modeling Study Implicating Abnormal Calcium Handling. J. Am. Coll. Cardiol., November 25, 2008; 52(22): 1782 - 1792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Rudy, M. J. Ackerman, D. M. Bers, C. E. Clancy, S. R. Houser, B. London, A. D. McCulloch, D. A. Przywara, R. L. Rasmusson, R. J. Solaro, et al. Systems Approach to Understanding Electromechanical Activity in the Human Heart: A National Heart, Lung, and Blood Institute Workshop Summary Circulation, September 9, 2008; 118(11): 1202 - 1211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Weinberg, S. Iravanian, and L. Tung Representation of Collective Electrical Behavior of Cardiac Cell Sheets Biophys. J., August 1, 2008; 95(3): 1138 - 1150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bebarova, T. O'Hara, J. L. M. C. Geelen, R. J. Jongbloed, C. Timmermans, Y. H. Arens, L.-M. Rodriguez, Y. Rudy, and P. G. A. Volders Subepicardial phase 0 block and discontinuous transmural conduction underlie right precordial ST-segment elevation by a SCN5A loss-of-function mutation Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H48 - H58. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Severi, E. Grandi, C. Pes, F. Badiali, F. Grandi, and A. Santoro Calcium and potassium changes during haemodialysis alter ventricular repolarization duration: in vivo and in silico analysis Nephrol. Dial. Transplant., April 1, 2008; 23(4): 1378 - 1386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Grandi, J. L. Puglisi, S. Wagner, L. S. Maier, S. Severi, and D. M. Bers Simulation of Ca-Calmodulin-Dependent Protein Kinase II on Rabbit Ventricular Myocyte Ion Currents and Action Potentials Biophys. J., December 1, 2007; 93(11): 3835 - 3847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Colli Franzone, L. F. Pavarino, S. Scacchi, and B. Taccardi Monophasic action potentials generated by bidomain modeling as a tool for detecting cardiac repolarization times Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2771 - H2785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Michailova, W. Lorentz, and A. McCulloch Modeling transmural heterogeneity of KATP current in rabbit ventricular myocytes Am J Physiol Cell Physiol, August 1, 2007; 293(2): C542 - C557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Vecchietti, E. Grandi, S. Severi, I. Rivolta, C. Napolitano, S. G. Priori, and S. Cavalcanti In silico assessment of Y1795C and Y1795H SCN5A mutations: implication for inherited arrhythmogenic syndromes Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H56 - H65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-S. Zhang, J. Tranquillo, V. Neplioueva, N. Bursac, and A. O. Grant Sodium channel kinetic changes that produce Brugada syndrome or progressive cardiac conduction system disease Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H399 - H407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Baher, Z. Qu, A. Hayatdavoudi, S. T. Lamp, M.-J. Yang, F. Xie, S. Turner, A. Garfinkel, and J. N. Weiss Short-term cardiac memory and mother rotor fibrillation Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H180 - H189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dong, X. Sun, A. A. Prinz, and H.-S. Wang Effect of simulated Ito on guinea pig and canine ventricular action potential morphology Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H631 - H637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. S. Chauhan, E. Downar, K. Nanthakumar, J. D. Parker, H. J. Ross, W. Chan, and P. Picton Increased ventricular repolarization heterogeneity in patients with ventricular arrhythmia vulnerability and cardiomyopathy: a human in vivo study Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H79 - H86. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. I. Keller, J.-S. Rougier, J. P. Kucera, N. Benammar, V. Fressart, P. Guicheney, A. Madle, M. Fromer, J. Schlapfer, and H. Abriel Brugada syndrome and fever: Genetic and molecular characterization of patients carrying SCN5A mutations Cardiovasc Res, August 15, 2005; 67(3): 510 - 519. [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]
|
|
|
|
 |
|
 C. E. Clancy and R. S. Kass Inherited and Acquired Vulnerability to Ventricular Arrhythmias: Cardiac Na+ and K+ Channels Physiol Rev, January 1, 2005; 85(1): 33 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Livshitz, K. Decker, G. Faber, T. O'Hara, J. Silva, Y. Rudy, K. H. W. J. ten Tusscher, D. Noble, P. J. Noble, and A. V. Panfilov Comments on "A model for human ventricular tissue" Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H453 - H453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E Conrath, R. Wilders, R. Coronel, J. M.T de Bakker, P. Taggart, J. R de Groot, and T. Opthof Intercellular coupling through gap junctions masks M cells in the human heart Cardiovasc Res, May 1, 2004; 62(2): 407 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Oikarinen, M. S. Nieminen, M. Viitasalo, L. Toivonen, S. Jern, B. Dahlof, R. B. Devereux, P. M. Okin, and for the LIFE Study Investigators QRS Duration and QT Interval Predict Mortality in Hypertensive Patients With Left Ventricular Hypertrophy: The Losartan Intervention for Endpoint Reduction in Hypertension Study Hypertension, May 1, 2004; 43(5): 1029 - 1034. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. E.C. Taes, N. H. Lameire, M. L. De Buyzere, A. Shoja, G. De Backer, and J. R. Delanghe Exercise-induced Myocardial Ischemia Is Accompanied by Increased Serum Creatine Concentrations Clin. Chem., April 1, 2003; 49(4): 684 - 686. [Full Text] [PDF]
|
|
|
|
|
|
S. Miyoshi, H. Mitamura, K. Fujikura, Y. Fukuda, K. Tanimoto, Y. Hagiwara, M. Ita, and S. Ogawa A mathematical model of phase 2 reentry: role of L-type Ca current Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1285 - H1294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. Pandit, W. R. Giles, and S. S. Demir A Mathematical Model of the Electrophysiological Alterations in Rat Ventricular Myocytes in Type-I Diabetes Biophys. J., February 1, 2003; 84(2): 832 - 841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Mazhari "Are We There Yet?!": Cardiac Channelopathy and Our Journey Toward Computational Medicine Circ. Res., May 3, 2002; 90(8): 842 - 843. [Full Text] [PDF]
|
|