Connexin-43 expression: A therapeutic target for the treatment of ventricular tachycardia

Craig Steven McLachlan, Zakaria Ali Moh Almsherqi, Brett Hambly, Mark McGuire

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Gap junctions (Gj) form conduits between adjacent cells that are composed of coannexin (Cx) protein subunits and allow direct intercellular communication. Specifically gap-junctional channels permit intercellular transfer of small molecules including second messengers and metabolites and allow for intercellular propagation of current-carrying ions between excitable cardiac myocytes. Pathological stimuli can cause cellular stress that affects intercellular communication by altering the abundance of functional gap junction channels. Significant changes in gap junction function may alter the velocity or anisotropy of cardiac conduction. The number of gap junctions (expressed Cx) per intercalated disk length and the number of cells connected by intercalated disks to a single myocyte are decreased within the acute myocardial infarct (MI) border zone as a result of ischemia. The gap junction surface area in hearts subjected to chronic hypertrophy is significantly decreased in both human and translational animal models. The concept of heterogeneity for connexin-43 expression across the ventricular myocardial wall is explored in the current chapter. MI ventricular remodeling increases connexin heterogeneity and the propensity for ventricular arrhythmias. Drug targets that alter the expression and function of connexin-43 post-MI are reviewed. A particular emphasis is placed on the role of nitric oxide modulation on connexin-43 expression.

Original languageEnglish
Title of host publicationCardiac Arrhythmias
Subtitle of host publicationFrom Basic Mechanism to State-of-the-Art Management
PublisherSpringer-Verlag London Ltd
Pages351-360
Number of pages10
ISBN (Electronic)9781447153160
ISBN (Print)1447153154, 9781447153153
DOIs
Publication statusPublished - 1 Nov 2013
Externally publishedYes

    Fingerprint

Keywords

  • Connexin 43
  • Gap-junctional modulation
  • Ventricular tachycardia

Cite this

McLachlan, C. S., Almsherqi, Z. A. M., Hambly, B., & McGuire, M. (2013). Connexin-43 expression: A therapeutic target for the treatment of ventricular tachycardia. In Cardiac Arrhythmias: From Basic Mechanism to State-of-the-Art Management (pp. 351-360). Springer-Verlag London Ltd. https://doi.org/10.1007/978-1-4471-5316-0_27