Adding a new dimension to cardiac nano-architecture using electron microscopy: coupling membrane excitation to calcium signaling.

Advances in microscopic imaging technologies and associated computational methods now allow descriptions of cellular anatomy to go beyond 2-dimensions, revealing new micro-domain dynamics at unprecedented resolutions. In cardiomyocytes, electron microscopy (EM) first described junctional membrane complexes between the sarcolemma and sarcoplasmic reticulum over a half-century ago. Since then, 3-dimensional EM technologies such as electron tomography have become successful in determining the realistic nano-geometry of membrane junctions (dyads and peripheral junctions) and associated structures such as transverse tubules (T-tubules, aka. T-system). Concomitantly, super-resolution light microscopy has gone beyond the diffraction-limit to determine the distribution of molecules, such as ryanodine receptors, with 10(-8) meter (10nm) order accuracy. This review provides the current structural perspective and functional interpretation of membrane junction complexes, which are the central machinery controlling cardiac excitation-contraction coupling via calcium signaling.