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April 1, 1997Journal of Clinical InvestigationOpen Access

Pharmacological targeting of long QT mutant sodium channels.

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Why the study?

Does mexiletine selectively suppress the defective behavior of mutant sodium channels in LQT3?

Population

Cultured human cells with heterologous expression of mutant voltage-gated cardiac sodium channels (LQT3)

Comparison

Mexiletine vs Wild type (WT) channels

Design

Preclinical

Authors

DWD W WangVanderbilt UniversityKYKazuto YazawaKagoshima UniversityNMNaomasa MakitaElectrophysiology

Discussion

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Implication

Mexiletine may target LQT3 defects at low doses; hypothesis-generating in animal models, clinical translation remains open.

Structured PICO

Does mexiletine selectively suppress the defective behavior of mutant sodium channels in LQT3?

P
Population
Cultured human cells with heterologous expression of mutant voltage-gated cardiac sodium channels (LQT3)
I
Intervention
Mexiletine
C
Comparator
Wild type (WT) channels
O
Outcome
Inhibition of late-opening channels (IC50)surrogate

Mexiletine selectively suppresses the late sodium current defect in LQT3 mutant channels at very low concentrations, providing a mechanistic basis for its therapeutic use in this specific long QT syndrome variant.

Cite This Study

Wang et al. (1997) studied this question.

synapsesocial.com/papers/6a6f7efbfe4101aa97dfcd9chttps://doi.org/10.1172/jci119335
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Also Consider

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

  1. 1External pH modifies sodium channel block by mexiletine in guinea pig ventricular myocytes1994 · 12 citations
  2. 2Evidence of genetic heterogeneity in Romano-Ward long QT syndrome. Analysis of 23 families.1994 · 83 citations
  3. 3Lidocaine block of cardiac sodium channels.1983 · 663 citations
  4. 4Blockade of rabbit atrial sodium channels by lidocaine. Characterization of continuous and frequency-dependent blocking.1989 · 62 citations
  5. 5Antiarrhythmic Agents: The Modulated Receptor Mechanism of Action of Sodium and Calcium Channel-Blocking Drugs1984 · 553 citations