Mutation-specific effects of lidocaine in Brugada syndrome

Colleen E Clancy, Xander H T Wehrens

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Brugada syndrome (BrS) is a hereditary cardiac disease characterized by right bundle-branch block, an elevation of the ST-segment in leads V1 through V3 on the electrocardiogram, and ventricular fibrillation that can lead to sudden cardiac death. Mutations in the cardiac sodium channel gene SCN5A, which encodes the α-subunit of the human cardiac voltage-dependent Na+ channel (Nav1.5), are identified in 15-30% of patients with BrS. Most SCN5A mutations lead to a 'loss-of-function' phenotype, reducing the Na+ current during the early phases of the action potential. Anti-arrhythmic drugs that affect Na+ channels typically block these Na+ channels, thereby exaggerating the ECG abnormalities and arrhythmogenicity in the BrS. However, the N406S mutation in SCN5A causes distinct gating defects and enhanced intermediate inactivation of Na+ channels, which led to unexpected pharmacological effects of lidocaine in a patient carrying this mutation. In the presence of the N406S mutation, use-dependent block by lidocaine is reduced and recovery from intermediate inactivation is hastened by lidocaine. These findings suggest that lidocaine may improve the Brugada phenotype in patients with N406S by increasing the availability of Na+ channels.

Original languageEnglish (US)
Pages (from-to)249-252
Number of pages4
JournalInternational Journal of Cardiology
Volume121
Issue number3
DOIs
StatePublished - Oct 18 2007
Externally publishedYes

Fingerprint

Brugada Syndrome
Lidocaine
Mutation
Electrocardiography
Phenotype
Inborn Genetic Diseases
Bundle-Branch Block
Sodium Channels
Anti-Arrhythmia Agents
Sudden Cardiac Death
Ventricular Fibrillation
Action Potentials
Heart Diseases
Pharmacology
Pharmaceutical Preparations
Genes

Keywords

  • Brugada syndrome
  • Lidocaine
  • Local anesthetics
  • Sodium channel
  • Sudden cardiac death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Mutation-specific effects of lidocaine in Brugada syndrome. / Clancy, Colleen E; Wehrens, Xander H T.

In: International Journal of Cardiology, Vol. 121, No. 3, 18.10.2007, p. 249-252.

Research output: Contribution to journalArticle

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