The evolution of patch-clamp electrophysiology: Robotic, multiplex, and dynamic

The patch-clamp technique has been the gold standard for analysis of excitable cells. Since its development in the 1980s, it has contributed immensely to our understanding of neurons, muscle cells, and cardiomyocytes and the ion channels and receptors that reside within them. This technique, predicated on Ohm's law, enables precise measurement of macroscopic excitability patterns and assessment of ionic and gating conductance, even to the single channel level. Over the years, patch-clamp electrophysiology has undergone extensive modifications, with the introduction of new applications that have enhanced its power and reach. The most recent evolution of this technique occurred with the introduction of robotic high-throughput automated platforms that enable high-quality simultaneous recordings, in both voltage- and current-clamp modes, from tens to hundreds of cells, including cells freshly isolated from their native tissues. Combined with new dynamic-clamp applications, these new methods provide increasingly powerful tools for studying the contributions of ion channels and receptors to electrogenesis. In this brief review, we provide an overview of these enhanced patch-clamp techniques, followed by some of the applications presently being pursued, and a perspective into the potential future of the patch-clamp method. SIGNIFICANCE STATEMENT: The patch-clamp technique, introduced in the 1980s, has revolutionized the understanding of electrogenesis. Predicated on Ohm's law, this approach facilitates exploration of ionic conductances, gating mechanisms of ion channels and receptors, and their roles in neuronal, muscular, and cardiac excitability. Robotic platforms for high-throughput patch-clamp and dynamic-clamp have recently expanded their reach. Here, we outline new advances in patch-clamp including high-throughput analysis of freshly isolated neurons and discuss the increasingly powerful trajectory of new patch-clamp techniques.