Dataset Information

Atrial-ventricular differences in rabbit cardiac voltage-gated Na⁺ currents: Basis for atrial-selective block by ranolazine.

ABSTRACT:

Background

Class 1 antiarrhythmic drugs are highly effective in restoring and maintaining sinus rhythm in atrial fibrillation patients but carry a risk of ventricular tachyarrhythmia. The antianginal agent ranolazine is a prototypic atrial-selective voltage-gated Na⁺ channel blocker but the mechanisms underlying its atrial-selective action remain unclear.

Objective

The present study examined the mechanisms underlying the atrial-selective action of ranolazine.

Methods

Whole-cell voltage-gated Na⁺ currents (I_Na) were recorded at room temperature (?22°C) from rabbit isolated left atrial and right ventricular myocytes.

Results

I_Na conductance density was ?1.8-fold greater in atrial than in ventricular cells. Atrial I_Na was activated at command potentials ?7 mV more negative and inactivated at conditioning potentials ?11 mV more negative than ventricular I_Na. The onset of inactivation of I_Na was faster in atrial cells than in ventricular myocytes. Ranolazine (30 ?M) inhibited I_Na in atrial and ventricular myocytes in a use-dependent manner consistent with preferential activated/inactivated state block. Ranolazine caused a significantly greater negative shift in voltage of half-maximal inactivation in atrial cells than in ventricular cells, the recovery from inactivation of I_Na was slowed by ranolazine to a greater extent in atrial myocytes than in ventricular cells, and ranolazine produced an instantaneous block that showed marked voltage dependence in atrial cells.

Conclusion

Differences exist between rabbit atrial and ventricular myocytes in the biophysical properties of I_Na. The more negative voltage dependence of I_Na activation and inactivation, together with trapping of the drug in the inactivated channel, underlies an atrial-selective action of ranolazine.

SUBMITTER: Caves RE

PROVIDER: S-EPMC5666337 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Atrial-ventricular differences in rabbit cardiac voltage-gated Na<sup>+</sup> currents: Basis for atrial-selective block by ranolazine.

Caves Rachel E RE Cheng Hongwei H Choisy Stéphanie C SC Gadeberg Hanne C HC Bryant Simon M SM Hancox Jules C JC James Andrew F AF

Heart rhythm 20170610 11

<h4>Background</h4>Class 1 antiarrhythmic drugs are highly effective in restoring and maintaining sinus rhythm in atrial fibrillation patients but carry a risk of ventricular tachyarrhythmia. The antianginal agent ranolazine is a prototypic atrial-selective voltage-gated Na<sup>+</sup> channel blocker but the mechanisms underlying its atrial-selective action remain unclear.<h4>Objective</h4>The present study examined the mechanisms underlying the atrial-selective action of ranolazine.<h4>Methods ...[more]

PMID: 28610990

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Dataset Information

Atrial-ventricular differences in rabbit cardiac voltage-gated Na⁺ currents: Basis for atrial-selective block by ranolazine.

Background

Objective

Methods

Results

Conclusion

Publications

Atrial-ventricular differences in rabbit cardiac voltage-gated Na<sup>+</sup> currents: Basis for atrial-selective block by ranolazine.

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Tweets

Dataset Information

Atrial-ventricular differences in rabbit cardiac voltage-gated Na+ currents: Basis for atrial-selective block by ranolazine.

Background

Objective

Methods

Results

Conclusion

Publications

Atrial-ventricular differences in rabbit cardiac voltage-gated Na<sup>+</sup> currents: Basis for atrial-selective block by ranolazine.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Atrial-ventricular differences in rabbit cardiac voltage-gated Na⁺ currents: Basis for atrial-selective block by ranolazine.