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January 1, 1988Circulation ResearchOpen Access

Transient outward current prominent in canine ventricular epicardium but not endocardium.

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Key result

A transient outward current (Ito) with slow (tau 350-570 msec) and fast (tau 41-85 msec) components significantly contributes to canine ventricular epicardial, but not endocardial, action potentials.

Population

Canine ventricular myocardium (epicardium and endocardium)

Comparison

Electrophysiological evaluation with 1-5 mM… vs Endocardium vs Epicardium; baseline vs…

Design

Preclinical

Authors

SLSilvio LitovskyCross-Cutting CardiologyCharles AntzelevitchCharles AntzelevitchElectrophysiology

Discussion

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Implication

Ito heterogeneity in canine ventricle warrants human studies; leaves open its role in clinical repolarization or arrhythmias.

Key Points

  • To determine whether a transient outward current contributes to action potential differences between the epicardial and endocardial layers of canine ventricular myocardium.
  • Recorded action potentials from canine ventricular epicardium and endocardium using conventional microelectrode techniques across varying stimulation rates.
  • Characterized phase 1 restitution kinetics and evaluated the effects of 4-aminopyridine (1–5 mM), ryanodine, and replacement of Ca2+ with Sr2+.
  • Epicardial action potentials exhibited a distinct 'spike and dome' morphology with a prominent phase 1 that became accentuated at slower rates, which was absent in endocardium.
  • Phase 1 restitution identified a slow recovery component (time constant: 350–570 ms) sensitive to 4-aminopyridine and a fast component (time constant: 41–85 ms) sensitive to 4-aminopyridine, ryanodine, and Sr2+.
  • Pharmacological inhibition of the transient outward current transformed the epicardial action potential configuration to resemble that of endocardium.

Structured PICO

P
Population
Canine ventricular myocardium (epicardium and endocardium)
I
Intervention
Electrophysiological evaluation with 1-5 mM 4-aminopyridine, ryanodine, and Sr2+ replacement of Ca2+
C
Comparator
Endocardium vs Epicardium; baseline vs post-intervention
O
Outcome
Action potential morphology and restitution of phase 1 amplitudesurrogate

Demonstrates the presence of a transient outward current (Ito) in canine ventricular epicardium but not endocardium, explaining the 'spike and dome' action potential morphology.

Cite This Study

Litovsky et al. (1988) studied Canine ventricular electrophysiology. 4-aminopyridine, ryanodine, and Sr2+ vs. Endocardium was evaluated on Action potential phase 1 amplitude restitution. A transient outward current (Ito) with slow (tau 350-570 msec) and fast (tau 41-85 msec) components significantly contributes to canine ventricular epicardial, but not endocardial, action potentials.

synapsesocial.com/papers/6a0e4e31bc348c84f2fd9a5dhttps://doi.org/10.1161/01.res.62.1.116
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Simultaneous recording of action potentials from endocardium and epicardium during ischemia in the isolated cat ventricle: relation of temporal electrophysiologic heterogeneities to arrhythmias.1986 · 121 citations
  2. 2Propagation of Impulses across the Purkinje Fiber-Muscle Junctions in the Dog Heart1970 · 171 citations
  3. 3The dependence of plateau currents in cardiac Purkinje fibres on the interval between action potentials1972 · 118 citations
  4. 4Effects of 4-aminopyridine on rate-related depression of cardiac action potentials1986 · 14 citations
  5. 5A transient outward current in isolated cells from the crista terminalis of rabbit heart.1985 · 166 citations