Abnormalities in Gap Junctions and Ca²⁺ Dynamics in Cardiomyocytes at the Border Zone of Myocardial Infarcts

Abstract

Abnormalities in gap junction function and Ca²⁺ dynamics are believed to be important factors in arrhythmogenesis after myocardial infarction. To elucidate the relationship between changes in Ca²⁺ dynamics and gap junctions, we analyzed by real-time in situ Ca²⁺ imaging of fluo-3 loaded whole hearts the spatiotemporal occurrence of Ca²⁺ waves and the localization of connexin43 (Cx43) at the border zone of myocardial infarcts induced in the rat by coronary ligation. At early time points (2-4 hours postligation), different regions of the left ventricle showed distinct changes in cytosolic free Ca²⁺ concentrations [Ca²⁺]_i. While some cardiomyocytes of infarcted regions exhibited high levels of resting fluo-3 fluorescence, at border zones frequent Ca²⁺ waves were observed. Some of the waves were abolished by spontaneous Ca²⁺ transients and others were not. Intact myocardium apart from infarcted regions exhibited homogenous Ca²⁺ transients. Confocal imaging of Cx43 and actin filaments in the rat heart fixed 2 hours after coronary ligation revealed that Cx43 was markedly decreased in the area of myocyte necrosis with contraction bands and in the neighboring myocardium. These results suggest that abnormal expression and function of gap junctions could be associated with Ca²⁺ waves at the border zone of myocardial infarcts, possibly through Ca²⁺ overload.

Key Words:

• Arrhythmia
• Ca²⁺ overload
• Ca²⁺ wave
• confocal microscopy
• connexin43