Cardiac conduction in isolated hearts of genetically modified mice - Connexin43 and salts

Physiologic variations in perfusate composition have been identified as a new and important modulator of cardiac conduction velocity (CV), particularly when gap junctions (GJ) are reduced. We recently demonstrated in ex vivo hearts that perfusates with low sodium and high potassium preferentially slow ventricular CV in mice genetically engineered to express 50% less of the gap junction protein, connexin43 (Cx43). We also reported the possible role of calcium in modulating CV. In this review we discuss previous murine studies that explored the CV-GJ relationship in isolated mouse heart preparations with approximately 50% reduced Cx43. Studies were grouped according to the type of perfusate utilized, and CV during GJ uncoupling was compared.Studies in Group A preferentially used perfusates with low sodium, high potassium and non-physiologic calcium, and found CV slows and arrhythmias increase in mouse hearts with reduced Cx43. Studies in Group B used solutions with high sodium, low potassium and physiologic calcium, and did not observe CV slowing nor increased arrhythmia risk with loss of Cx3. Studies in Group C used solutions with low sodium, low potassium, physiologic calcium, creatine, taurine, and insulin. CV slowing was not observed, nor was arrhythmia risk increased with loss of Cx43.We suggest that perfusate ion composition may be a major determinant of whether CV slows when Cx43 is reduced. Furthermore, the review of these studies highlights important theoretical developments in the understanding of cardiac conduction and suggests that ionic milieu can conceal electrophysiologic remodeling secondary to reduced Cx43 expression as occurs in many cardiac diseases.