(Circulation. 1996;93:168-177.)
© 1996 American Heart Association, Inc.
Articles |
Regional Differences in Current Density and Rate-Dependent Properties of the Transient Outward Current in Subepicardial and Subendocardial Myocytes of Human Left Ventricle
Presented in part at the 66th Scientific Sessions of the American Heart Association, Atlanta, Ga, November 8-11, 1993, and published in abstract form in Circulation (1993;88[suppl I]:I-89).
From the Departments of Medicine I (M.N., G.S.) and Cardiovascular Surgery (P.Ü.), University of Munich, and the Department of Medicine III, University of Cologne (D.J.B.), Cologne, Germany.
Correspondence to Dr Michael Näbauer, Medizinische Klinik I, Klinikum Großhadern, 81377 Munich, Germany.
Background Recordings of outward currents in human ventricular myocytes revealed the presence of a large calcium-insensitive transient outward current. This current has been suggested to contribute significantly to regional electrophysiological heterogeneity in myocardial cells and tissue of several animal species and to cause electrical gradients across the ventricular wall.
Methods and Results The patch-clamp technique was used to record action potentials and outward currents in myocytes enzymatically isolated from thin subepicardial and subendocardial layers of human nonfailing and failing left ventricle. In all subepicardial cells studied, a calcium-insensitive transient outward current (Ito1) could be recorded with large density (10.6±1.08 pA/pF at 40 mV), whereas current density of Ito1 in subendocardial cells was fourfold smaller (2.63±0.31 pA/pF, P<.0001, nonfailing myocardium). In failing hearts, the density of Ito1 was significantly smaller in subepicardial cells (7.81±0.53 pA/pF, P=.012) but not different in subendocardial myocytes (2.01±0.23 pA/pF, P=.25). Rate-dependent reduction of peak Ito1 at a 2-Hz depolarization rate was minimal in subepicardial cells (to 92.3±1.9%), whereas peak Ito1 in subendocardial myocytes was almost suppressed at 2 Hz (reduction to 13.2±2.1%, P<.0001). The different rate-dependent reduction of the transient outward current was due to a much slower time course of recovery from inactivation in subendocardial cells. Kinetic data, including action potentials recorded at 35°C, allow assessment of the role of the transient outward current for electrical activity and transmural voltage gradients in human left ventricle.
Conclusions Marked regional differences in density and rate-dependent properties of the transient outward current exist in subendocardial and subepicardial layers in human left ventricular myocardium, causing transmural electrical gradients that are important for normal and pathological electrical behavior of the human heart. The difference in recovery rates of the transient outward current is a distinguishing feature between subepicardial and subendocardial myocytes.
Key Words: action potentials • electrophysiology • heart failure • ventricles
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Y. A. Kuryshev, G. M. Brittenham, H. Fujioka, P. Kannan, C.-C. Shieh, S. A. Cohen, and A. M. Brown Decreased Sodium and Increased Transient Outward Potassium Currents in Iron-Loaded Cardiac Myocytes : Implications for the Arrhythmogenesis of Human Siderotic Heart Disease Circulation, August 10, 1999; 100(6): 675 - 683. [Abstract] [Full Text] [PDF]
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P. Schaffer, B. Pelzmann, E. Bernhart, P. Lang, H. Machler, B. Rigler, and B. Koidl Repolarizing currents in ventricular myocytes from young patients with tetralogy of Fallot Cardiovasc Res, August 1, 1999; 43(2): 332 - 343. [Abstract] [Full Text] [PDF]
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E. Carmeliet Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias Physiol Rev, July 1, 1999; 79(3): 917 - 1017. [Abstract] [Full Text] [PDF]
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A. C.G. van Ginneken and M. W. Veldkamp Implications of inhomogeneous distribution of IKS and IKr channels in ventricle with respect to effects of class III agents and beta-agonists Cardiovasc Res, July 1, 1999; 43(1): 20 - 22. [Full Text] [PDF]
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J. Cheng, K. Kamiya, W. Liu, Y. Tsuji, J. Toyama, and I. Kodama Heterogeneous distribution of the two components of delayed rectifier K+ current: a potential mechanism of the proarrhythmic effects of methanesulfonanilideclass III agents Cardiovasc Res, July 1, 1999; 43(1): 135 - 147. [Abstract] [Full Text] [PDF]
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J van der Velden, L.J Klein, M van der Bijl, M.A.J.M Huybregts, W Stooker, J Witkop, L Eijsman, C.A Visser, F.C Visser, and G.J.M Stienen Isometric tension development and its calcium sensitivity in skinned myocyte-sized preparations from different regions of the human heart Cardiovasc Res, June 1, 1999; 42(3): 706 - 719. [Abstract] [Full Text] [PDF]
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A. D. Wickenden, T. J. Jegla, R. Kaprielian, and P. H. Backx Regional contributions of Kv1.4, Kv4.2, and Kv4.3 to transient outward K+ current in rat ventricle Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1599 - H1607. [Abstract] [Full Text] [PDF]
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G. F. Tomaselli and E. Marban Electrophysiological remodeling in hypertrophy and heart failure Cardiovasc Res, May 1, 1999; 42(2): 270 - 283. [Full Text] [PDF]
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D. M. Roden and S. Kupershmidt From genes to channels: normal mechanisms Cardiovasc Res, May 1, 1999; 42(2): 318 - 326. [Abstract] [Full Text] [PDF]
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D. J Snyders Structure and function of cardiac potassium channels Cardiovasc Res, May 1, 1999; 42(2): 377 - 390. [Abstract] [Full Text] [PDF]
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S. M Bryant, S.J. Shipsey, and G. Hart Normal regional distribution of membrane current density in rat left ventricle is altered in catecholamine-induced hypertrophy Cardiovasc Res, May 1, 1999; 42(2): 391 - 401. [Abstract] [Full Text] [PDF]
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F. Aimond, J. L Alvarez, J.-M. Rauzier, P. Lorente, and G. Vassort Ionic basis of ventricular arrhythmias in remodeled rat heart during long-term myocardial infarction Cardiovasc Res, May 1, 1999; 42(2): 402 - 415. [Abstract] [Full Text] [PDF]
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U. C. Hoppe, D. C. Johns, E. Marban, and B. O'Rourke Manipulation of Cellular Excitability by Cell Fusion : Effects of Rapid Introduction of Transient Outward K+ Current on the Guinea Pig Action Potential Circ. Res., April 30, 1999; 84(8): 964 - 972. [Abstract] [Full Text] [PDF]
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R. L. Winslow, J. Rice, S. Jafri, E. Marban, and B. O'Rourke Mechanisms of Altered Excitation-Contraction Coupling in Canine Tachycardia-Induced Heart Failure, II : Model Studies Circ. Res., March 19, 1999; 84(5): 571 - 586. [Abstract] [Full Text] [PDF]
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S. G. Priori, J. Barhanin, R. N. W. Hauer, W. Haverkamp, H. J. Jongsma, A. G. Kleber, W. J. McKenna, D. M. Roden, Y. Rudy, K. Schwartz, et al. Genetic and Molecular Basis of Cardiac Arrhythmias: Impact on Clinical Management Part III Circulation, February 9, 1999; 99(5): 674 - 681. [Full Text] [PDF]
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I. Gussak, C. Antzelevitch, P. Bjerregaard, J. A. Towbin, and B. R. Chaitman The Brugada syndrome: clinical, electrophysiologic and genetic aspects J. Am. Coll. Cardiol., January 1, 1999; 33(1): 5 - 15. [Abstract] [Full Text] [PDF]
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J. Brugada, P. Brugada, and R. Brugada The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death--the Brugada syndrome Europace, January 1, 1999; 1(3): 156 - 166. [Abstract] [PDF]
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G.-R. Li, B. Yang, J. Feng, R. F. Bosch, M. Carrier, and S. Nattel Transmembrane ICa contributes to rate-dependent changes of action potentials in human ventricular myocytes Am J Physiol Heart Circ Physiol, January 1, 1999; 276(1): H98 - H106. [Abstract] [Full Text] [PDF]
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W. Kong, S. Po, T. Yamagishi, M. D. Ashen, G. Stetten, and G. F. Tomaselli Isolation and characterization of the human gene encoding Ito: further diversity by alternative mRNA splicing Am J Physiol Heart Circ Physiol, December 1, 1998; 275(6): H1963 - H1970. [Abstract] [Full Text] [PDF]
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S. M. Bryant, X. Wan, S.J. Shipsey, and G. Hart Regional differences in the delayed rectifier current (IKr and IKs) contribute to the differences in action potential duration in basal left ventricular myocytes in guinea-pig Cardiovasc Res, November 1, 1998; 40(2): 322 - 331. [Abstract] [Full Text] [PDF]
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S. Kaab, J. Dixon, J. Duc, D. Ashen, M. Nabauer, D. J. Beuckelmann, G. Steinbeck, D. McKinnon, and G. F. Tomaselli Molecular Basis of Transient Outward Potassium Current Downregulation in Human Heart Failure : A Decrease in Kv4.3 mRNA Correlates With a Reduction in Current Density Circulation, October 6, 1998; 98(14): 1383 - 1393. [Abstract] [Full Text] [PDF]
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G.-R. Li, J. Feng, L. Yue, and M. Carrier Transmural heterogeneity of action potentials and Ito1 in myocytes isolated from the human right ventricle Am J Physiol Heart Circ Physiol, August 1, 1998; 275(2): H369 - H377. [Abstract] [Full Text] [PDF]
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L. Priebe and D. J. Beuckelmann Simulation Study of Cellular Electric Properties in Heart Failure Circ. Res., June 15, 1998; 82(11): 1206 - 1223. [Abstract] [Full Text] [PDF]
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B. Pelzmann, P. Schaffer, E. Bernhart, P. Lang, H. Machler, B. Rigler, and B. Koidl L-type calcium current in human ventricular myocytes at a physiological temperature from children with tetralogy of Fallot Cardiovasc Res, May 1, 1998; 38(2): 424 - 432. [Abstract] [Full Text] [PDF]
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R. F. Bosch, R. Gaspo, A. E. Busch, H. J. Lang, G.-R. Li, and S. Nattel Effects of the chromanol 293B, a selective blocker of the slow, component of the delayed rectifier K+ current, on repolarization in human and guinea pig ventricular myocytes Cardiovasc Res, May 1, 1998; 38(2): 441 - 450. [Abstract] [Full Text] [PDF]
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