Affiliation:
1. 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.
Abstract
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 (I
to1
) could be recorded with large density (10.6±1.08 pA/pF at 40 mV), whereas current density of I
to1
in subendocardial cells was fourfold smaller (2.63±0.31 pA/pF,
P
<.0001, nonfailing myocardium). In failing hearts, the density of I
to1
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 I
to1
at a 2-Hz depolarization rate was minimal in subepicardial cells (to 92.3±1.9%), whereas peak I
to1
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
393 articles.
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