The transient outward current and action potential notch are
smaller in left vs right canine ventricular epicardium.
Diego, Jose M. Di, Zhuo-Qian Sun, and Charles Antzelevitch.
Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica,
NY 13501-1787
APStracts 3:0066H, 1996.
Transmural heterogeneities in the contribution of repolarizing
currents have been shown to underlie prominent differences in the
electrophysiology and pharmacology of ventricular epicardial,
endocardial and M cells in a number of species. The degree to which
heterogeneities exist between the right and left ventricles is not
well appreciated. The present study uses standard microelectrode and
whole cell patch clamp techniques to contrast the
electrophysiological characteristics and pharmacological
responsiveness of tissues and myocytes isolated from right (RVE) and
left (LVE) canine ventricular epicardium. RVE and LVE studied under
nearly identical conditions displayed major differences in the early
repolarizing phases of the action potential. The magnitude of phase 1
in RVE was nearly 3 fold that in LVE (28.7+6.2 mV vs 10.6+4.1 mV;
basic cycle length = 2000 msec). Phase 1 in RVE was also more
sensitive to alterations of the stimulation rate and to 4
-aminopyridine (4-AP), suggesting a much greater contribution of the
transient outward current (Ito1) in RVE vs. LVE. ( phase 1 amplitude
analysis, previously shown to provide a reasonable estimate of the
availability and kinetics of reactivation of Ito1, revealed two
exponential components of recovery: a fast component ((50 msec) that
was diminished by 4-AP, ryanodine and low chloride; and a slow
component ((350 msec) that was abolished following exposure to 4-AP,
but was unaffected by ryanodine or low chloride. The combination of
4-AP plus either ryanodine, low chloride or DIDS (chloride channel
blocker) completely eliminated the spike and dome morphology of the
action potential and all rate dependence of the early phases of the
action potential, making RVE and LVE indistinguishable. Ito1 was
measured using voltage steps to potentials between 0 and +70 mV from
a holding potential of -80 mV (preceded by a 10 msec step to -45 mV
to inactivate INa and in the presence of CdCl2 to block ICa ). At +70
mV, RVE myocytes displayed peak Ito1 densities ranging between 28 and
37 pA/pF. LVE myocytes included cells with similar Ito1 densities
(thought to represent subsurface cells) but also cells with much
smaller current levels (thought to represent surface cells). Average
peak Ito1 density was significantly smaller in LVE vs. RVE at all
voltages > +10 mV. Our data point to prominent differences in
the magnitude of the Ito1-mediated action potential notch in cells at
the surface of right vs left canine ventricular epicardium and
suggest that important distinctions may exist in the response of
these two tissues to pharmacologic agents and pathophysiologic
states, as previously demonstrated for epicardium and endocardium.
Our findings also suggest that a calcium-activated outward current
contributes to the early repolarization phase in both right and left
ventricular epicardium and that the influence of this current,
although small, is relatively more important in the left ventricle.
Received 16 February 1995; accepted in final form 25 January
1996.
APS Manuscript Number H147-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 14 February 96