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September 1, 1994Circulation Research366 citationsOpen Access

Transient outward current in human ventricular myocytes of subepicardial and subendocardial origin.

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EWErich WettwerGAG J AmosHPHerbert Posival

Key Result

Transient outward current density at +60 mV was larger in human subepicardial cells (7.9 +/- 0.7 pA/pF) than in subendocardial cells (2.3 +/- 0.3 pA/pF).

Key Points

  • This research aims to explore the differences in transient outward current (Ito) between human ventricular myocytes from subepicardial and subendocardial regions.
  • Human ventricular myocytes were isolated from subepicardial and subendocardial tissue.
  • Comparative analyses were performed on Ito across different heart conditions, including failing and nonfailing donor hearts.
  • Measurement of action potentials and current densities was conducted.
  • Subepicardial myocytes exhibited larger Ito at +60 mV (7.9 +/- 0.7 pA/pF) compared to subendocardial myocytes (2.3 +/- 0.3 pA/pF).
  • Subendocardial Ito was larger in nonfailing hearts versus failing hearts, with no differences observed in subepicardial cells.
  • The potential of half-maximal activation was significantly more positive in subendocardial cells (+25.6 +/- 3.5 mV) than in subepicardial cells (+9.2 +/- 1.8 mV).

Structured PICO

P
Population
Human ventricular myocytes isolated from separated subepicardial (n=28) and subendocardial (n=16) tissue from explanted failing and nonfailing donor hearts.
I
Intervention
Electrophysiological characterization of transient outward current (Ito).
C
Comparator
Comparison between subepicardial and subendocardial cells, and between cells from failing and nonfailing hearts.
O
Outcome
Regional variations in transient outward current (Ito) density and kinetics.surrogate

Significant regional differences exist in the transient outward current between human subepicardial and subendocardial ventricular myocytes, which may have implications for arrhythmogenesis in heart failure.

Main Result

Absolute Event Rate: 7.9% vs 2.3%

Abstract

In various mammalian species, shapes of action potentials vary within the cardiac wall because of differences in transient outward current (Ito). A prominent Ito exists in human ventricular myocytes, but cells have not been separated according to their original localization. Human ventricular myocytes were isolated from separated subepicardial and subendocardial tissue, and regional variations in Ito were studied. Ito was larger in subepicardial than subendocardial cells. Current density at +60 mV was 7.9 +/- 0.7 pA/pF (n = 28) in subepicardial cells and 2.3 +/- 0.3 pA/pF (n = 16) in subendocardial cells. When cells from explanted failing and nonfailing donor hearts were compared, Ito was not different in subepicardial cells; however, it was larger in subendocardial cells from nonfailing hearts. The potential of half-maximal activation (V0.5) was more positive in subendocardial cells (+25.6 +/- 3.5 mV, n = 15) than in subepicardial cells (+9.2 +/- 1.8 mV, n = 28). There was no difference in V0.5 between cells from failing and nonfailing hearts. Ito inactivation was similar in all cell types and independent of membrane depolarization (time constant tau = approximately 60 milliseconds at 22 degrees C). The potential of half-maximal steady-state inactivation was similar in all cell types. Recovery from inactivation of Ito was fast in subepicardial cells at -100 mV (tau = 24 +/- 4 milliseconds, n = 6), exceeding control values transiently (overshoot), and slow at -40 mV without overshoot (tau = 638 +/- 91 milliseconds, n = 6). In subendocardial cells, Ito recovered at -100 mV with a fast phase (tau = 25 milliseconds) and a slow phase (tau = 328 milliseconds), and recovery was not complete after 6 seconds at -100 mV. In conclusion, regional differences in Ito between subepicardial and subendocardial cells may have clinical implications with respect to rhythmic disturbance during heart failure.

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Cite This Study

Wettwer et al. (1994) studied Heart failure. Subepicardial origin vs. Subendocardial origin was evaluated on Current density at +60 mV. Transient outward current density at +60 mV was larger in human subepicardial cells (7.9 +/- 0.7 pA/pF) than in subendocardial cells (2.3 +/- 0.3 pA/pF).

synapsesocial.com/papers/6a0883c37de338f10b10bee8https://doi.org/10.1161/01.res.75.3.473
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