What question did this study set out to answer?

To determine whether cardiac glycoside inhibition of electrogenic Na-K pump current involves high-affinity binding sites in guinea pig ventricular myocytes.

June 1, 1989Circulation ResearchOpen Access

Inhibition of Na-K pump current in guinea pig ventricular myocytes by dihydroouabain occurs at high- and low-affinity sites.

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Population

Guinea pig ventricular myocytes

Comparison

Dihydroouabain at nine concentrations vs Steady-state holding current before external…

Design

Preclinical

Authors

DMDavid J. MogulIllinois Institute of Technology HRH RasmussenElectrophysiology DSD H SingerNorthwestern University

Discussion

Member takes

Implication

Delineates dual-affinity Na-K pump inhibition in guinea pig myocytes; leaves open translation to human cardiac glycoside effects.

Key Points

To determine whether cardiac glycoside inhibition of electrogenic Na-K pump current involves high-affinity binding sites in guinea pig ventricular myocytes.
Isolated guinea pig ventricular myocytes were voltage-clamped at -40 mV at 34 °C with internal Na+ activity fixed at approximately 30 mM using wide-pore patch pipettes.
The change in steady-state holding current before and during exposure to nine dihydroouabain (DHO) concentrations (0.01 to 1,000 µM) was measured and normalized to cellular membrane capacitance.
Dihydroouabain showed no effect on baseline membrane conductance at a holding potential of -40 mV.
Inhibition of Na-K pump current followed a biphasic concentration dependence well fitted to a two-binding site model, yielding inhibitory KD values of 0.05 µM for the high-affinity site and 64.5 µM for the low-affinity site.

Structured PICO

Population

Guinea pig ventricular myocytes

Intervention

Dihydroouabain (DHO) at nine concentrations (range, 0.01-1,000 microM)

Comparator

Steady-state holding current before external exposure to DHO

Outcome

Concentration dependence of the inhibition of Na-K pump current (Ipump)surrogate

Dihydroouabain inhibits the electrogenic properties of the Na-K pump in guinea pig ventricular myocytes by binding to both high- and low-affinity sites.

Cite This Study

Mogul et al. (1989) studied this question.

synapsesocial.com/papers/6a73c492f96a1419040dd29b https://doi.org/10.1161/01.res.64.6.1063

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Inhibition of Na-K pump current in guinea pig ventricular myocytes by dihydroouabain occurs at high- and low-affinity sites.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Inhibition of Na-K pump current in guinea pig ventricular myocytes by dihydroouabain occurs at high- and low-affinity sites.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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