Fibroblast-specific deletion of Connexin43 significantly reduced the maximal signal amplitude of electrotonic conduction in cardiac scar tissue to 12% compared to 61% in wild-type controls.
Non-myocytes in ventricular scar tissue electrically couple to surrounding myocytes to support passive conduction of action potentials, a process dependent on Connexin43 expression.
Absolute Event Rate: 12% vs 61%
p-value: p=<0.05
Studies have demonstrated non-myocytes, including fibroblasts, can electrically couple to myocytes in culture. However, evidence demonstrating current can passively spread across scar tissue in the intact heart remains elusive. We hypothesize electrotonic conduction occurs across non-myocyte gaps in the heart and is partly mediated by Connexin43 (Cx43). We investigated whether non-myocytes in ventricular scar tissue are electrically connected to surrounding myocardial tissue in wild type and fibroblast-specific protein-1 driven conditional Cx43 knock-out mice (Cx43fsp1KO). Electrical coupling between the scar and uninjured myocardium was demonstrated by injecting current into the myocardium and recording depolarization in the scar through optical mapping. Coupling was significantly reduced in Cx43fsp1KO hearts. Voltage signals were recorded using microelectrodes from control scars but no signals were obtained from Cx43fsp1KO hearts. Recordings showed significantly decreased amplitude, depolarized resting membrane potential, increased duration and reduced upstroke velocity compared to surrounding myocytes, suggesting that the non-excitable cells in the scar closely follow myocyte action potentials. These results were further validated by mathematical simulations. Optical mapping demonstrated that current delivered within the scar could induce activation of the surrounding myocardium. These data demonstrate non-myocytes in the scar are electrically coupled to myocytes, and coupling depends on Cx43 expression.
Mahoney et al. (2016) studied Cardiac scar tissue / Myocardial injury. Fibroblast-specific deletion of Connexin43 (Cx43fsp1KO) vs. Littermate Cx43flox/flox Cre negative mice (controls) was evaluated on Maximal signal amplitude in the scar relative to the myocardium near the electrode (p=<0.05). Fibroblast-specific deletion of Connexin43 significantly reduced the maximal signal amplitude of electrotonic conduction in cardiac scar tissue to 12% compared to 61% in wild-type controls.