Cardiac Na+ channels as therapeutic targets for antiarrhythmic agents

I. W. Glaaser, Colleen E Clancy

Research output: Chapter in Book/Report/Conference proceedingChapter

13 Citations (Scopus)

Abstract

There are many factors that influence drug block of voltage-gated Na+ channels (VGSC). Pharmacological agents vary in conformation, charge, and affinity. Different drugs have variable affinities to VGSC isoforms, and drug efficacy is affected by implicit tissue properties such as resting potential, action potential morphology, and action potential frequency. The presence of polymorphisms and mutations in the drug target can also influence drug outcomes. While VGSCs have been therapeutic targets in the management of cardiac arrhythmias, their potential has been largely overshadowed by toxic side effects. Nonetheless, many VGSC blockers exhibit inherent voltage- and use-dependent properties of channel block that have recently proven useful for the diagnosis and treatment of genetic arrhythmias that arise from defects in Na+ channels and can underlie idiopathic clinical syndromes. These defective channels suggest themselves as prime targets of disease and perhaps even mutation specific pharmacological interventions.

Original languageEnglish (US)
Title of host publicationHandbook of Experimental Pharmacology
Pages99-121
Number of pages23
Volume171
DOIs
StatePublished - 2006
Externally publishedYes

Publication series

NameHandbook of Experimental Pharmacology
Volume171
ISSN (Print)01712004
ISSN (Electronic)18650325

Fingerprint

Pharmaceutical Preparations
Action Potentials
Cardiac Arrhythmias
Pharmacology
Therapeutics
Mutation
Poisons
Electric potential
Polymorphism
Membrane Potentials
Conformations
Protein Isoforms
Tissue
Defects

Keywords

  • Antiarrhythmic
  • Brugada Syndrome
  • CAST
  • Channelopathies
  • Conduction disorders
  • CYP
  • Cytochrome enzymes
  • Flecainide
  • Isoform specificity
  • Lidocaine
  • Local anesthetic
  • Long-QT Syndrome
  • Molecular determinants
  • Mutation
  • Na 1.1
  • Na+ channel blocker
  • Na1.5
  • Pharmacodynamics
  • Pharmacokinetics
  • Polymorphism
  • Proarrhythmic
  • Recovery from block
  • SCN1A
  • SCN5A
  • Sicilian Gambit
  • Singh-Vaughan Williams
  • Structural determinants
  • Tonic block
  • TTX
  • Use-dependent block
  • VGSC

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry

Cite this

Glaaser, I. W., & Clancy, C. E. (2006). Cardiac Na+ channels as therapeutic targets for antiarrhythmic agents. In Handbook of Experimental Pharmacology (Vol. 171, pp. 99-121). (Handbook of Experimental Pharmacology; Vol. 171). https://doi.org/10.1007/3-540-29715-4-4

Cardiac Na+ channels as therapeutic targets for antiarrhythmic agents. / Glaaser, I. W.; Clancy, Colleen E.

Handbook of Experimental Pharmacology. Vol. 171 2006. p. 99-121 (Handbook of Experimental Pharmacology; Vol. 171).

Research output: Chapter in Book/Report/Conference proceedingChapter

Glaaser, IW & Clancy, CE 2006, Cardiac Na+ channels as therapeutic targets for antiarrhythmic agents. in Handbook of Experimental Pharmacology. vol. 171, Handbook of Experimental Pharmacology, vol. 171, pp. 99-121. https://doi.org/10.1007/3-540-29715-4-4
Glaaser IW, Clancy CE. Cardiac Na+ channels as therapeutic targets for antiarrhythmic agents. In Handbook of Experimental Pharmacology. Vol. 171. 2006. p. 99-121. (Handbook of Experimental Pharmacology). https://doi.org/10.1007/3-540-29715-4-4
Glaaser, I. W. ; Clancy, Colleen E. / Cardiac Na+ channels as therapeutic targets for antiarrhythmic agents. Handbook of Experimental Pharmacology. Vol. 171 2006. pp. 99-121 (Handbook of Experimental Pharmacology).
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