© 1996 American Heart Association, Inc.
Articles |
Two Components of Delayed Rectifier Current in Canine Atrium and Ventricle
Does IKs Play a Role in the Reverse Rate Dependence of ClassIII Agents?
Abstract Because the number and characteristics of delayed rectifier K+ current (IK) components vary between species, the role of each component in the action potential and modulation by class III agents is uncertain. To address these issues, IK was assessed in adult isolated canine ventricular and atrial myocytes by using whole-cell and perforated-patch techniques. IK components were characterized by using two complementary approaches: a kinetic approach (based on biexponential fits to deactivating tail currents) and a pharmacological approach (using the methanesulfonanilide compound E-4031). In ventricular myocytes, two exponential tail current components were distinguished; these components differed in the voltage and time dependence of activation and the effect of lower [K+]o. Both kinetic components contributed equally to peak tail current amplitude (measured at -35 mV) after a single 300-ms pulse to 5 mV, simulating an action potential. By use of E-4031, rapidly and slowly activating components of IK (IKr and IKs, respectively) that were analogous to tail components described kinetically were identified. The activation kinetics and rectification properties of canine IKr and IKs are qualitatively similar to those described previously for guinea pigs. In contrast, canine IKr and IKs deactivation kinetics differed markedly from those found in guinea pigs, with canine IKr deactivating slowly (time constant
, 2 to 3 s near -35 mV) and
IKs deactivating rapidly (, 150 ms near -35 mV and
decreasing to 30 ms near -85 mV). E-4031 elicited reverse
rate-dependent effects (greater drug-induced prolongation of
the action potential at slower stimulation rates); this effect is
inconsistent with the hypothesis attributing reverse rate
dependence to incomplete IKs deactivation during rapid
stimulation (due to rapid deactivation of canine IKs). Two
IK components with characteristics comparable to those
found in ventricular myocytes were also observed in atrial
myocytes. In conclusion, (1) IKr- and IKs-like
components of IK are present in canine atrial and
ventricular myocytes, with deactivation kinetics strikingly
different from those found in guinea pigs, and (2) the rapid
deactivation kinetics of canine IKs do not support its role
in reverse rate dependence with class III agents in this species.
Key Words: delayed rectifier K+ currents • E-4031 • reverse rate dependence • ventricular myocytes • atrial myocytes
This article has been cited by other articles:
 |
|
 |
|
  A. Sridhar, Y. Nishijima, D. Terentyev, R. Terentyeva, R. Uelmen, M. Kukielka, I. M. Bonilla, G. A. Robertson, S. Gyorke, G. E. Billman, et al. Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2008; 295(5): R1463 - R1472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Roden Repolarization Reserve: A Moving Target Circulation, September 2, 2008; 118(10): 981 - 982. [Full Text] [PDF]
|
|
|
|
|
|
D. M. Roden and T. Yang Protecting the Heart Against Arrhythmias: Potassium Current Physiology and Repolarization Reserve Circulation, September 6, 2005; 112(10): 1376 - 1378. [Full Text] [PDF]
|
|
|
|
|
|
N. Jost, L. Virag, M. Bitay, J. Takacs, C. Lengyel, P. Biliczki, Z. Nagy, G. Bogats, D. A. Lathrop, J. G. Papp, et al. Restricting Excessive Cardiac Action Potential and QT Prolongation: A Vital Role for IKs in Human Ventricular Muscle Circulation, September 6, 2005; 112(10): 1392 - 1399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. X. Liu, J. Zhou, S. Nattel, and G. Koren Single-channel recordings of a rapid delayed rectifier current in adult mouse ventricular myocytes: basic properties and effects of divalent cations J. Physiol., April 15, 2004; 556(2): 401 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. B. Rasmussen, M. Moller, H.-G. Knaus, B. S. Jensen, S.-P. Olesen, and N. K. Jorgensen Subcellular localization of the delayed rectifier K+ channels KCNQ1 and ERG1 in the rat heart Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1300 - H1309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Stengl, P. G A Volders, M. B Thomsen, R. L H M G Spatjens, K. R Sipido, and M. A Vos Accumulation of slowly activating delayed rectifier potassium current (IKs) in canine ventricular myocytes J. Physiol., September 15, 2003; 551(3): 777 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G.A. Volders, M. Stengl, J. M. van Opstal, U. Gerlach, R. L.H.M.G. Spatjens, J. D.M. Beekman, K. R. Sipido, and M. A. Vos Probing the Contribution of IKs to Canine Ventricular Repolarization: Key Role for {beta}-Adrenergic Receptor Stimulation Circulation, June 3, 2003; 107(21): 2753 - 2760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Xu, J. J. Salata, J. Wang, Y. Wu, G.-X. Yan, T. Liu, R. A. Marinchak, and P. R. Kowey Increasing IKs corrects abnormal repolarization in rabbit models of acquired LQT2 and ventricular hypertrophy Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H664 - H670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsuura, T. Ehara, W.-G. Ding, M. Omatsu-Kanbe, and T. Isono Rapidly and slowly activating components of delayed rectifier K+ current in guinea-pig sino-atrial node pacemaker cells J. Physiol., May 1, 2002; 540(3): 815 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Vornanen, A. Ryokkynen, and A. Nurmi Temperature-dependent expression of sarcolemmal K+ currents in rainbow trout atrial and ventricular myocytes Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R1191 - R1199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Malik, P Farbom, V Batchvarov, K Hnatkova, and A J Camm Relation between QT and RR intervals is highly individual among healthy subjects: implications for heart rate correction of the QT interval Heart, March 1, 2002; 87(3): 220 - 228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Lu, K. Kamiya, T. Opthof, K. Yasui, and I. Kodama Density and Kinetics of IKr and IKs in Guinea Pig and Rabbit Ventricular Myocytes Explain Different Efficacy of IKs Blockade at High Heart Rate in Guinea Pig and Rabbit: Implications for Arrhythmogenesis in Humans Circulation, August 21, 2001; 104(8): 951 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Virag, N. Iost, M. Opincariu, J. Szolnoky, J. Szecsi, G. Bogats, P. Szenohradszky, A. Varro, and J. Gy. Papp The slow component of the delayed rectifier potassium current in undiseased human ventricular myocytes Cardiovasc Res, March 1, 2001; 49(4): 790 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jiang, C. Cabo, J.-A. Yao, P. A Boyden, and G.-N. Tseng Delayed rectifier K currents have reduced amplitudes and altered kinetics in myocytes from infarcted canine ventricle Cardiovasc Res, October 1, 2000; 48(1): 34 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Merot, V. Probst, M. Debailleul, U. Gerlach, N. S. Moise, H. Le Marec, and F. Charpentier Electropharmacological characterization of cardiac repolarization in German shepherd dogs with an inherited syndrome of sudden death: abnormal response to potassium channel blockers J. Am. Coll. Cardiol., September 1, 2000; 36(3): 939 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Gintant Characterization and functional consequences of delayed rectifier current transient in ventricular repolarization Am J Physiol Heart Circ Physiol, March 1, 2000; 278(3): H806 - H817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Varro, B. Balati, N. Iost, J. Takacs, L. Virag, D. A Lathrop, L. Csaba, L. Talosi, and J. G. Papp The role of the delayed rectifier component IKs in dog ventricular muscle and Purkinje fibre repolarization J. Physiol., February 15, 2000; 523(1): 67 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Barajas-Martinez, A. Elizalde, and J. A. Sanchez-Chapula Developmental differences in delayed rectifying outward current in feline ventricular myocytes Am J Physiol Heart Circ Physiol, February 1, 2000; 278(2): H484 - H492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Lynch Jr, M. S. Houle, G. L. Stump, A. A. Wallace, D. B. Gilberto, H. Jahansouz, G. R. Smith, A. J. Tebben, N. J. Liverton, H. G. Selnick, et al. Antiarrhythmic Efficacy of Selective Blockade of the Cardiac Slowly Activating Delayed Rectifier Current, IKs, in Canine Models of Malignant Ischemic Ventricular Arrhythmia Circulation, November 2, 1999; 100(18): 1917 - 1922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jiang, W. Dun, and G.-N. Tseng Mechanism for the effects of extracellular acidification on HERG-channel function Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1283 - H1292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 X.-K. Liu, A. Katchman, S. N. Ebert, and R. L. Woosley The Antiestrogen Tamoxifen Blocks the Delayed Rectifier Potassium Current, IKr, in Rabbit Ventricular Myocytes J. Pharmacol. Exp. Ther., December 1, 1998; 287(3): 877 - 883. [Abstract] [Full Text]
|
|
|
|
|
|
N. Iost, L. Virag, M. Opincariu, J. Szecsi, Andras Varro, and J. Gy. Papp Delayed rectifier potassium current in undiseased human ventricular myocytes Cardiovasc Res, December 1, 1998; 40(3): 508 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Babij, G. R. Askew, B. Nieuwenhuijsen, C.-M. Su, T. R. Bridal, B. Jow, T. M. Argentieri, J. Kulik, L. J. DeGennaro, W. Spinelli, et al. Inhibition of Cardiac Delayed Rectifier K+ Current by Overexpression of the Long-QT Syndrome HERG G628S Mutation in Transgenic Mice Circ. Res., September 21, 1998; 83(6): 668 - 678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-K. Liu, A. Katchman, M.-D. Drici, S. N. Ebert, I. Ducic, M. Morad, and R. L. Woosley Gender Difference in the Cycle Length-Dependent QT and Potassium Currents in Rabbits J. Pharmacol. Exp. Ther., May 1, 1998; 285(2): 672 - 679. [Abstract] [Full Text]
|
|
|
|
|
|
B. Drolet, M. Khalifa, P. Daleau, B. A. Hamelin, and J. Turgeon Block of the Rapid Component of the Delayed Rectifier Potassium Current by the Prokinetic Agent Cisapride Underlies Drug-Related Lengthening of the QT Interval Circulation, January 20, 1998; 97(2): 204 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ren, G. A. Gintant, R. E. Miller, and A. J. Davidoff High extracellular glucose impairs cardiac E-C coupling in a glycosylation-dependent manner Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2876 - H2883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. London, M. C. Trudeau, K. P. Newton, A. K. Beyer, N. G. Copeland, D. J. Gilbert, N. A. J enkins, C. A. Satler, and G. A. Robertson Two Isoforms of the Mouse Ether-a-go-go–Related Gene Coassemble to Form Channels With Properties Similar to the Rapidly Activating Component of the Cardiac Delayed Rectifier K+ Current Circ. Res., November 19, 1997; 81(5): 870 - 878. [Abstract] [Full Text]
|
|
|
|
|
|
C. Fiset, B. Drolet, B. A. Hamelin, and J. Turgeon Block of IKs by the Diuretic Agent Indapamide Modulates Cardiac Electrophysiological Effects of the Class III Antiarrhythmic Drug dl-Sotalol J. Pharmacol. Exp. Ther., October 1, 1997; 283(1): 148 - 156. [Abstract] [Full Text]
|
|
|
|
|
|
R. S. Wymore, G. A. Gintant, R. T. Wymore, J. E. Dixon, D. McKinnon, and I. S. Cohen Tissue and Species Distribution of mRNA for the IKr-like K+ Channel, erg Circ. Res., February 1, 1997; 80(2): 261 - 268. [Abstract] [Full Text]
|
|
|
|
|
|
L. Wang, Z.-P. Feng, C. S. Kondo, R. S. Sheldon, and H. J. Duff Developmental Changes in the Delayed Rectifier K+ Channels in Mouse Heart Circ. Res., July 1, 1996; 79(1): 79 - 85. [Abstract] [Full Text]
|
|