|
|
|
|
|
|
|
||
The Journal of General Physiology, Vol 96, 835-863, Copyright © 1990 by The Rockefeller University Press
ARTICLES |
JR Balser, PB Bennett and DM Roden
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Several conflicting models have been used to characterize the gating behavior of the cardiac delayed rectifier. In this study, whole-cell delayed rectifier currents were measured in voltage-clamped guinea pig ventricular myocytes, and a minimal model which reproduced the observed kinetic behavior was identified. First, whole-cell potassium currents between -10 and +70 mV were recorded using external solutions designed to eliminate Na and Ca currents and two components of time-dependent outward current were found. One component was a La3(+)-sensitive current which inactivated and resembled the transient outward current described in other cell types; single-channel observations confirmed the presence of a transient outward current in these guinea pig ventricular cells (gamma = 9.9 pS, [K]o = 4.5 mM). Analysis of envelopes of tail amplitudes demonstrated that this component was absent in solutions containing 30-100 microM La3+. The remaining time- dependent current, IK, activated with a sigmoidal time course that was well-characterized by three time constants. Nonlinear least-squares fits of a four-state Markovian chain model (closed - closed - closed - open) to IK activation were therefore compared to other models previously used to characterize IK gating: n2 and n4 Hodgkin-Huxley models and a Markovian chain model with only two closed states. In each case the four-state model was significantly better (P less than 0.05). The failure of the Hodgkin-Huxley models to adequately describe the macroscopic current indicates that identical and independent gating particles should not be assumed for this K channel. The voltage- dependent terms describing the rate constants for the four-state model were then derived using a global fitting approach for IK data obtained over a wide range of potentials (-80 to +70 mV). The fit was significantly improved by including a term representing the membrane dipole forces (P less than 0.01). The resulting rate constants predicted long single-channel openings (greater than 1 s) at voltages greater than 0 mV. In cell-attached patches, single delayed rectifier channels which had a mean chord conductance of 5.4 pS at +60 mV ([K]o = 4.5 mM) were recorded for brief periods. These channels exhibited behavior predicted by the four-state model: long openings and latency distributions with delayed peaks. These results suggest that the cardiac delayed rectifier undergoes at least two major transitions between closed states before opening upon depolarization.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  D. M. Roden Repolarization Reserve: A Moving Target Circulation, September 2, 2008; 118(10): 981 - 982. [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Nerbonne and R. S. Kass Molecular Physiology of Cardiac Repolarization Physiol Rev, October 1, 2005; 85(4): 1205 - 1253. [Abstract] [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]
|
|
|
|
 |
|
 J. Temple, P. Frias, J. Rottman, T. Yang, Y. Wu, E. E. Verheijck, W. Zhang, C. Siprachanh, H. Kanki, J. B. Atkinson, et al. Atrial Fibrillation in KCNE1-Null Mice Circ. Res., July 8, 2005; 97(1): 62 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Bian, A. Kagan, and T. V. McDonald Molecular analysis of PIP2 regulation of HERG and IKr Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2154 - H2163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Mullins, S. Z. Stepanovic, R. R. Desai, A. L. George Jr., and J. R. Balser Extracellular Sodium Interacts with the HERG Channel at an Outer Pore Site J. Gen. Physiol., September 30, 2002; 120(4): 517 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Ideker, J. Huang, V. Fast, and W. M. Smith Recent Fibrillation Studies: Attempts to Wrest Order From Disorder Circ. Res., December 7, 2001; 89(12): 1089 - 1091. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kaab and M. Nabauer Diversity of ion channel expression in health and disease Eur. Heart J. Suppl., September 1, 2001; 3(suppl_K): K31 - K40. [Abstract] [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]
|
|
|
|
 |
|
 D. J Snyders Structure and function of cardiac potassium channels Cardiovasc Res, May 1, 1999; 42(2): 377 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Khalifa, B. Drolet, P. Daleau, C. Lefez, M. Gilbert, S. Plante, G. E. O'Hara, O. Gleeton, B. A. Hamelin, and J. Turgeon Block of Potassium Currents in Guinea Pig Ventricular Myocytes and Lengthening of Cardiac Repolarization in Man by the Histamine H1 Receptor Antagonist Diphenhydramine J. Pharmacol. Exp. Ther., February 1, 1999; 288(2): 858 - 865. [Abstract] [Full Text]
|
|
|
|
|
|
S. Kupershmidt, T. Yang, and D. M. Roden Modulation of Cardiac Na+ Current Phenotype by ß1-Subunit Expression Circ. Res., August 24, 1998; 83(4): 441 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Daleau, M. Khalifa, and J. Turgeon Effects of Cadmium and Nisoldipine on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes J. Pharmacol. Exp. Ther., May 1, 1997; 281(2): 826 - 833. [Abstract] [Full Text]
|
|
|
|
|
|
N. K. Jurkiewicz, J. Wang, B. Fermini, M. C. Sanguinetti, and J. J. Salata Mechanism of Action Potential Prolongation by RP 58866 and Its Active Enantiomer, Terikalant: Block of the Rapidly Activating Delayed Rectifier K+ Current, IKr Circulation, December 1, 1996; 94(11): 2938 - 2946. [Abstract] [Full Text]
|
|
|
|
|
|
M.-L. Roy, R. Dumaine, and A. M. Brown HERG, a Primary Human Ventricular Target of the Nonsedating Antihistamine Terfenadine Circulation, August 15, 1996; 94(4): 817 - 823. [Abstract] [Full Text]
|
|
|
|
|
|
M. V. Brahmajothi, M. J. Morales, S. Liu, R. L. Rasmusson, D. L. Campbell, and H. C. Strauss In Situ Hybridization Reveals Extensive Diversity of K+ Channel mRNA in Isolated Ferret Cardiac Myocytes Circ. Res., June 1, 1996; 78(6): 1083 - 1089. [Abstract] [Full Text]
|
|
|
|
|
|
G. A. Gintant Two Components of Delayed Rectifier Current in Canine Atrium and Ventricle : Does IKs Play a Role in the Reverse Rate Dependence of ClassIII Agents? Circ. Res., January 1, 1996; 78(1): 26 - 37. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. K. England, V. N. Uebele, J. Kodali, P. B. Bennett, and M. M. Tamkun A Novel K[IMAGE] Channel beta-Subunit (hKvbeta1.3) Is Produced via Alternative mRNA Splicing J. Biol. Chem., December 1, 1995; 270(48): 28531 - 28534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yang, S. Kupershmidt, and D. M. Roden Anti-minK Antisense Decreases the Amplitude of the Rapidly Activating Cardiac Delayed Rectifier K+ Current Circ. Res., December 1, 1995; 77(6): 1246 - 1253. [Abstract] [Full Text]
|
|
|
|
|
|
J. Zeng, K. R. Laurita, D. S. Rosenbaum, and Y. Rudy Two Components of the Delayed Rectifier K+ Current in Ventricular Myocytes of the Guinea Pig Type : Theoretical Formulation and Their Role in Repolarization Circ. Res., July 1, 1995; 77(1): 140 - 152. [Abstract] [Full Text]
|
|
|
|
|
|
T. Yang, D. J. Snyders, and D. M. Roden Ibutilide, a Methanesulfonanilide Antiarrhythmic, Is a Potent Blocker of the Rapidly Activating Delayed Rectifier K+ Current (IKr) in AT-1 Cells : Concentration-, Time-, Voltage-, and Use-Dependent Effects Circulation, March 15, 1995; 91(6): 1799 - 1806. [Abstract] [Full Text]
|
|
|
|
|
|
E. Delpon, C. Valenzuela, O. Perez, O. Casis, and J. Tamargo Propafenone Preferentially Blocks the Rapidly Activating Component of Delayed Rectifier K+ Current in Guinea Pig Ventricular Myocytes : Voltage-Independent and Time-Dependent Block of the Slowly Activating Component Circ. Res., February 1, 1995; 76(2): 223 - 235. [Abstract] [Full Text]
|
|
|
|
|
|
J. J. Salata, N. K. Jurkiewicz, A. A. Wallace, R. F. Stupienski III, P. J. Guinosso Jr, and J. J. Lynch Jr Cardiac Electrophysiological Actions of the Histamine H1-Receptor Antagonists Astemizole and Terfenadine Compared With Chlorpheniramine and Pyrilamine Circ. Res., January 1, 1995; 76(1): 110 - 119. [Abstract] [Full Text]
|
|
|
|
