Electrical Behavior At the Transverse-Axial Tubular Membrane of Hypertrophic Cardiomyocytes in Situ

Abstract

Cardiac hypertrophy is associated with restructuring of the transverse-axial tubular (TAT) system. It is unknown whether such changes are accompanied by altered electrical behavior at the transverse-axial tubules. Here, we used confocal microscopy and the voltage-sensitive dye ANNINE-6plus to visualize the TAT network and to resolve action potentials at the surface and TAT membrane of in situ left ventricular cardiomyocytes within normal and hypertrophic mouse hearts. Transgenic (TG) hearts overexpressing Gαq and non-transgenic (NTG) hearts were perfused in Langendorff-mode during image acquisition. Cardiomyocytes in hypertrophic TG hearts exhibited patchy loss and gain, respectively, of transverse and axial elements. Action potentials were recorded at the TAT membrane within two adjacent cardiomyocytes (denoted T1 and T2) and at the end-to-end junctions (E) between them. Action potential onset occurred synchronously within the TAT network of NTG and TG cardiomyocytes. Whereas the repolarization time course was similar between the three recording sites in NTG or TG hearts (Figure A), overall repolarization was prolonged in TG cardiomyocytes (Figure B). Thus, electrical coupling between the surface and TAT membrane was maintained despite pronounced TAT membrane restructuring in this model of cardiac hypertrophy.View Large Image | View Hi-Res Image | Download PowerPoint Slide