| Summary: | Optical electrophysiology techniques possess many advantages over standard electrode-based techniques, such as the ability to address many cells at once with high spatial resolution and a lower degree of invasiveness. Unfortunately, many of these optical methods have not been translated into human use for a variety of reasons. Our studies demonstrate that indocyanine green (ICG), an infrared dye that is already FDA-approved for clinical use, is voltage-sensitive, thus providing a novel strategy for assessing nervous function in humans. In addition to optically monitoring excitability, a clinical method for optically stimulating excitable cells could also be of great benefit. A primary limitation of current optical stimulus techniques is that they require genetic manipulation, which is not currently practical in humans. We have developed a novel tool based on the selective binding of gold nanoparticles to particular classes of excitable cells. This technique provides much of the power of current optical stimulus methods but requires no genetic modification of the subject. While optical electrophysiology holds great potential for future clinical applications, new optical methods can also help answer long-standing questions in basic science. A question of particular interest in ion channel biophysics concerns the single-molecule dynamics of protein voltage sensors. We have used two different approaches in an attempt to investigate this question and have obtained the first single-molecule recordings of voltage sensor movement. With further development, these methods could answer many questions that have thus far proven difficult to address with current techniques.
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