Novel Imaging Techniques in Cardiac Ion Channel Research

Abstract

Light microscopy has long been at the forefront of biological research, perhaps most significantly in the form of fluorescence microscopy. This technique, paired with the ongoing discovery and synthesis of increasingly brilliant fluorophores, allows for visualization of the internal machinations of cells with molecular specificity. However, until recently, a persistent limitation of fluorescence microscopy—the diffraction of visible light—has restricted elucidation of the subcellular organization and localization of molecules to spatial resolutions of 200–300 nanometers. The invention and implementation of several super-resolution fluorescence microscopies (SRFMs) over the last 10 years have circumvented this diffraction limit and allowed up to tenfold improvements in resolution. Applications of SRFM in cardiology research have already illuminated aspects of the cardiac nanoscale architecture which were previously unobservable, opening the door for new avenues of research. These discoveries include the sub-diffraction structure of the intercalated disk, the t-tubular network, and excitation-contraction coupling. In this chapter we will review SRFM methodologies, present some examples of their successful application in cardiac research, and discuss the techniques’ advantages, ongoing challenges, and future potential.