Extracellular sodium and potassium levels modulate cardiac conduction in mice heterozygous null for the Connexin43 gene

Sharon A. George, Katherine J. Sciuto, Joyce Lin, Mohamed E. Salama, James P. Keener, Robert G. Gourdie, Steven Poelzing

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Several studies have disagreed on measurements of cardiac conduction velocity (CV) in mice with a heterozygous knockout of the connexin gene Gja1—a mutation that reduces the gap junction (GJ) protein, Connexin43 (Cx43), by 50 %. We noted that perfusate ionic composition varied between studies and hypothesized that extracellular ionic concentration modulates CV dependence on GJs. CV was measured by optically mapping wild-type (WT) and heterozygous null (HZ) hearts serially perfused with solutions previously associated with no change (Solution 1) or CV slowing (Solution 2). In WT hearts, CV was similar for Solutions 1 and 2. However, consistent with the hypothesis, Solution 2 in HZ hearts slowed transverse CV (CVT) relative to Solution 1. Previously, we showed CV slowing in a manner consistent with ephaptic conduction correlated with increased perinexal inter-membrane width (WP) at GJ edges. Thus, WP was measured following perfusion with systematically adjusted [Na+]o and [K+]o in Solutions 1 and 2. A wider WP was associated with reduced CVT in WT and HZ hearts, with the greatest effect in HZ hearts. Increasing [Na+]o increased CVT only in HZ hearts. Increasing [K+]o slowed CVT in both WT and HZ hearts with large WP but only in HZ hearts with narrow WP. Conclusion: When perinexi are wide, decreasing excitability by modulating [Na+]o and [K+]o increases CV sensitivity to reduced Cx43. By contrast, CV is less sensitive to Cx43 and ion composition when perinexi are narrow. These results are consistent with cardiac conduction dependence on both GJ and non-GJ (ephaptic) mechanisms.

Original languageEnglish (US)
Pages (from-to)2287-2297
Number of pages11
JournalPflugers Archiv European Journal of Physiology
Volume467
Issue number11
DOIs
StatePublished - Nov 1 2015

Keywords

  • Conduction
  • Connexin43
  • Edema
  • Potassium
  • Sodium

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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