Abstract
1. Gradients of ion channels across the left ventricular (LV) wall have been well characterized and it has been shown that disruption of such gradients leads to altered rates of repolarization across the wall, which is associated with the generation of arrhythmias. 2. We have hypothesized that a transmural gradient of I(Na) is present and have directly measured this current in adult rat myocytes isolated from both the epicardial and endocardial layers of the left ventricle. Currents were also recorded in right ventricular (RV) myocytes for comparison. 3. Peak inward I(Na) currents, at -30 mV, were -49.7 +/- 2.5 pA pF(-1) (n = 22), -32.9 +/- 3.2 pA pF(-1) (n = 16) and -49.7 +/- 3.7 pA pF(-1) (n = 24) for RV, LV epicardial and LV endocardial myocytes, respectively. No differences in the voltage dependence of inactivation, the voltage dependence of steady-state inactivation, or reactivation were reported. 4. Our results demonstrate that a gradient of sodium current density is present across the LV wall of adult rat hearts.
MeSH Terms
Age Factors
Animals
Heart Ventricles/cytology,metabolism
Membrane Potentials/physiology
Muscle Fibers, Skeletal/metabolism
Myocardium/cytology,metabolism
Patch-Clamp Techniques
Rats
Rats, Sprague-Dawley
Sodium/metabolism
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ashamalla S M
Department of Physiology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Navarro D
Ward C A
References (24)
24 references, click to expand
-
Functional, structural, and dynamic basis of electrical heterogeneity in healthy and diseased cardiac muscle: implications for arrhythmogenesis and anti-arrhythmic drug therapy.
Pharmacol Ther. 1999 Nov;84(2):207-31
PMID: 10596907
-
Sodium channel block with mexiletine is effective in reducing dispersion of repolarization and preventing torsade des pointes in LQT2 and LQT3 models of the long-QT syndrome.
Circulation. 1997 Sep 16;96(6):2038-47
PMID: 9323097
-
Long QT syndrome.
Cardiol Clin. 2000 May;18(2):309-25
PMID: 10849875
-
Effects of BDF 9198 on action potentials and ionic currents from guinea-pig isolated ventricular myocytes.
Br J Pharmacol. 2000 Aug;130(8):1753-66
PMID: 10952663
-
Molecular pharmacology of the sodium channel mutation D1790G linked to the long-QT syndrome.
Circulation. 2000 Aug 22;102(8):921-5
PMID: 10952963
-
Protein kinase C-dependent modulation of Na+ currents increases the excitability of rat neocortical pyramidal neurones.
J Physiol. 2000 Oct 15;528 Pt 2:291-304
PMID: 11034619
-
Distribution of a persistent sodium current across the ventricular wall in guinea pigs.
Circ Res. 2000 Nov 10;87(10):910-4
PMID: 11073887
-
Larger late sodium conductance in M cells contributes to electrical heterogeneity in canine ventricle.
Am J Physiol Heart Circ Physiol. 2001 Aug;281(2):H689-97
PMID: 11454573
-
Transient outward current prominent in canine ventricular epicardium but not endocardium.
Circ Res. 1988 Jan;62(1):116-26
PMID: 2826039
-
Rate dependence of action potential duration and refractoriness in canine ventricular endocardium differs from that of epicardium: role of the transient outward current.
J Am Coll Cardiol. 1989 Oct;14(4):1053-66
PMID: 2551947
-
Electrophysiological properties and responses to simulated ischemia in cat ventricular myocytes of endocardial and epicardial origin.
Circ Res. 1990 Feb;66(2):469-77
PMID: 2297813
-
Ionic bases for electrophysiological distinctions among epicardial, midmyocardial, and endocardial myocytes from the free wall of the canine left ventricle.
Circ Res. 1993 Mar;72(3):671-87
PMID: 8431990
-
Phenotypic characterization of a novel long-QT syndrome mutation (R1623Q) in the cardiac sodium channel.
Circulation. 1998 Feb 24;97(7):640-4
PMID: 9495298
-
Transient outward current, Ito1, is altered in cardiac memory.
Circulation. 1999 Apr 13;99(14):1898-905
PMID: 10199889
-
Persistent T-wave changes after alteration of the ventricular activation sequence. New insights into cellular mechanisms of 'cardiac memory'.
Circulation. 1993 Oct;88(4 Pt 1):1811-9
PMID: 8403326
-
Molecular mechanism for an inherited cardiac arrhythmia.
Nature. 1995 Aug 24;376(6542):683-5
PMID: 7651517
-
Electrophysiologic characteristics of M cells in the canine left ventricular free wall.
J Cardiovasc Electrophysiol. 1995 Aug;6(8):591-603
PMID: 8535556
-
Multiple mechanisms of Na+ channel--linked long-QT syndrome.
Circ Res. 1996 May;78(5):916-24
PMID: 8620612
-
Evidence for the presence of M cells in the guinea pig ventricle.
J Cardiovasc Electrophysiol. 1996 Jun;7(6):503-11
PMID: 8743756
-
Characterization of human cardiac Na+ channel mutations in the congenital long QT syndrome.
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13200-5
PMID: 8917568
-
Phosphorylation of S1505 in the cardiac Na+ channel inactivation gate is required for modulation by protein kinase C.
J Gen Physiol. 1996 Nov;108(5):375-9
PMID: 8923263
-
Regional differences in the regulation of intracellular sodium and in action potential configuration in rabbit left ventricle.
Pflugers Arch. 1997 Feb;433(4):515-22
PMID: 9000431
-
Ionic mechanism of the effects of hydrogen peroxide in rat ventricular myocytes.
J Physiol. 1997 May 1;500 ( Pt 3):631-42
PMID: 9161981
-
Transmural dispersion of repolarization and arrhythmogenicity: the Brugada syndrome versus the long QT syndrome.
J Electrocardiol. 1999;32 Suppl:158-65
PMID: 10688320