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January 1, 1996Circulation Research

Two Components of Delayed Rectifier Current in Canine Atrium and Ventricle

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Key result

Canine IKr and IKs components exhibit deactivation kinetics strikingly different from guinea pigs, with rapid IKs deactivation not supporting its role in reverse rate dependence with class III agents.

Population

Adult isolated canine ventricular and atrial myocytes

Design

Preclinical

Authors

GGGary A. GintantElectrophysiology

Discussion

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Implication

Challenges guinea pig-based IKs models for class III agents; leaves open reverse rate dependence mechanisms in canines.

Structured PICO

P
Population
Adult isolated canine ventricular and atrial myocytes
I
Intervention
Pharmacological approach using E-4031 (a methanesulfonanilide compound) and kinetic approach using whole-cell and perforated-patch techniques
O
Outcome
Characterization of delayed rectifier K+ current (IK) components, specifically activation and deactivation kinetics of IKr and IKssurrogate

The study demonstrates that canine IKr and IKs have distinct deactivation kinetics compared to guinea pig models, challenging the hypothesis that incomplete IKs deactivation is responsible for reverse rate dependence seen with class III antiarrhythmic agents.

Cite This Study

Gary A. Gintant (1996) studied this question. E-4031 was evaluated on Delayed rectifier K+ current (IK) components (IKr and IKs) characteristics. Canine IKr and IKs components exhibit deactivation kinetics strikingly different from guinea pigs, with rapid IKs deactivation not supporting its role in reverse rate dependence with class III agents.

synapsesocial.com/papers/6a161081dca1af9bedbf8cf4https://doi.org/10.1161/01.res.78.1.26
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Also Consider

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

  1. 1Regional differences in IK density in canine left ventricle: role of IK,s in electrical heterogeneity1995 · 53 citations
  2. 2Contribution of Delayed Rectifier and Inward Rectifier to Repolarization of the Action Potential: Pharmacologic Separation1992 · 21 citations
  3. 3Electrophysiologic Effects of a New Class III Antiarrhythmic Agent, E-4031, on Atrial Flutter, Atrial Refractoriness, and Conduction Delay in a Canine Sterile Pericarditis Model1993 · 9 citations
  4. 4Time-dependent outward current in guinea pig ventricular myocytes. Gating kinetics of the delayed rectifier.1990 · 107 citations
  5. 5Characterization of two distinct depolarization-activated K+ currents in isolated adult rat ventricular myocytes.1991 · 295 citations