Connexin-43 Expression: A Therapeutic Target for the Treatment of Ventricular Tachycardia

  • Craig Steven McLachlan
  • Zakaria Ali Moh Almsherqi
  • Brett Hambly
  • Mark McGuire
Chapter
First Online:

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.

Keywords

Connexin 43 Ventricular tachycardia Gap-junctional modulation 
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Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  • Craig Steven McLachlan
    • 1
  • Zakaria Ali Moh Almsherqi
    • 2
  • Brett Hambly
    • 3
  • Mark McGuire
    • 4
  1. 1.Rural Clinical School, Faculty of MedicineUniversity of New South WalesSydneyAustralia
  2. 2.Department of PhysiologyNational University of SingaporeSingaporeSingapore
  3. 3.Department of PathologyUniversity of SydneyDarlingtonAustralia
  4. 4.Department of CardiologyRoyal Prince Alfred HospitalCamperdownAustralia

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