| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Department of Physiology and Biophysics, University of Calgary Health Sciences Centre, Calgary, Alberta, Canada T2N 4N1; 2Laboratoire de Genomique Fonctionnelle, Centre National de la Recherche Scientifique UPR 2580, and Institut de Genetique Humaine, Centre National de la Recherche Scientifique UPR 1142, 34396 Montpellier Cedex 5, France; and 3Department of Internal Medicine, Karl-Franzens-University Hospital, 8036 Graz, Austria
Submitted 6 August 2003 ; accepted in final form 17 December 2003
We have investigated the physiological role of the "rapidly activating" delayed rectifier K+ current (IKr) in pacemaker activity in isolated sinoatrial node (SAN) myocytes and the expression of mouse ether-a-go-go (mERG) genes in the adult mouse SAN. In isolated, voltage-clamped SAN cells, outward currents evoked by depolarizing steps (greater than –40 mV) were strongly inhibited by the class III methanesulfonanilide compound E-4031 (1–2.5 µM), and the deactivation "tail" currents that occurred during repolarization to a membrane potential of –45 mV were completely blocked. E-4031-sensitive currents (IKr) reached a maximum at a membrane potential of –10 mV and showed pronounced inward rectification at more-positive membrane potentials. Activation of IKr occurred at –40 to 0 mV, with half-activation at about –24 mV. The contribution of IKr to action potential repolarization and diastolic depolarization was estimated by determining the E-4031-sensitive current evoked during voltage clamp with a simulated mouse SAN action potential. IKr reached its peak value (
0.6 pA/pF) near –25 mV, close to the midpoint of the repolarization phase of the simulated action potential, and deactivated almost completely during the diastolic interval. E-4031 (1 µM) slowed the spontaneous pacing rate of Langendorff-perfused, isolated adult mouse hearts by an average of 36.5% (n = 5). Expression of mRNA corresponding to three isoforms coded by the mouse ERG1 gene (mERG1), mERG1a, mERG1a', and mERG1b, was consistently found in the SAN. Our data provide the first detailed characterization of IKr in adult mouse SAN cells, demonstrate that this current plays an important role in pacemaker activity, and indicate that multiple isoforms of mERG1 can contribute to native SAN IKr.
sinus node; E-4031; mERG1
This article has been cited by other articles:
|
|
 |
|
  E. J. White, S. J. Park, J. A. Foster, and J. D. Huizinga Ether-a-go-go-related gene 3 is the main candidate for the E-4031-sensitive potassium current in the pacemaker interstitial cells of Cajal Am J Physiol Gastrointest Liver Physiol, October 1, 2008; 295(4): G691 - G699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Mangoni and J. Nargeot Genesis and Regulation of the Heart Automaticity Physiol Rev, July 1, 2008; 88(3): 919 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mewe, I. Wulfsen, A. M. E. Schuster, R. Middendorff, G. Glassmeier, J. R. Schwarz, and C. K. Bauer Erg K+ channels modulate contractile activity in the bovine epididymal duct Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R895 - R904. [Abstract] [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]
|
|
|
|
 |
|
 A. Nygren, A. E. Lomax, and W. R. Giles Heterogeneity of action potential durations in isolated mouse left and right atria recorded using voltage-sensitive dye mapping Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2634 - H2643. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
