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August 1, 1996AJP Heart and Circulatory Physiology247 citations

I(to) and action potential notch are smaller in left vs. right canine ventricular epicardium

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JDJosé M. Di DiegoZSZhuoqian SunCACharles Antzelevitch

Key Result

The magnitude of phase 1 of the action potential in canine right ventricular epicardium was nearly threefold that in left ventricular epicardium (28.7 +/- 6.2 vs. 10.6 +/- 4.1 mV).

Structured PICO

P
Population
Tissues and myocytes isolated from right (RVE) and left canine ventricular epicardium (LVE)
E
Exposure
Electrophysiological characterization and pharmacological testing (4-aminopyridine, ryanodine, low chloride, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid)
C
Comparator
Right vs. left ventricular epicardium
O
Outcome
Magnitude of phase 1 action potential notch and transient outward current (I(to) 1) densitysurrogate

Significant electrophysiological heterogeneities exist between right and left canine ventricular epicardium, primarily driven by differences in transient outward current (I(to) 1).

Main Result

Absolute Event Rate: 28.7% vs 10.6%

Abstract

Transmural heterogeneities of repolarizing currents 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 canine ventricular epicardium (LVE). 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 threefold that in LVE: 28.7 +/- 6.2 vs. 10.6 +/- 4.1 mV (basic cycle length = 2,000 ms). 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 (I(to) 1) in RVE than in LVE. The combination of 4-AP plus ryanodine, low chloride, or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (chloride channel blocker) completely eliminated the notch and all rate dependence of the early phases of the action potential, making RVE and LVE indistinguishable. At +70 mV, RVE myocytes displayed peak I(to) 1 densities between 28 and 37 pA/pF. LVE myocytes included cells with similar I(to) 1 densities (thought to represent subsurface cells) but also cells with much smaller current levels (thought to represent surface cells). Average peak I(to) 1 density was significantly smaller in LVE than in RVE at voltages more than or equal to +10 mV. Our data point to prominent differences in the magnitude of the I(to) 1-mediated action potential notch in cells at the surface of RVE compared with the LVE and suggest that important distinctions may exist in the response of these two tissues to pharmacological agents and pathophysiological 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 RVE and LVE and that the influence of this current, although small, is more important in the left ventricle.

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Cite This Study

Diego et al. (1996) studied this question. Right ventricular epicardium (RVE) vs. Left ventricular epicardium (LVE) was evaluated on Magnitude of phase 1 of the action potential. The magnitude of phase 1 of the action potential in canine right ventricular epicardium was nearly threefold that in left ventricular epicardium (28.7 +/- 6.2 vs. 10.6 +/- 4.1 mV).

synapsesocial.com/papers/6a24519f003b3cd7fea65f36https://doi.org/10.1152/ajpheart.1996.271.2.h548
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