A force controlled patch clamp of beating cardiac cells

From its invention in the 1970s, the patch clamp technique is the gold standard in electrophysiology research and drug screening because it is the only tool enabling accurate investigation of voltage-gated ion channels, which are responsible for action potentials. Because of its key role in drug screening, innovation efforts are being made to reduce its complexity toward more automated systems. While some of these new approaches are being adopted in pharmaceutical companies, conventional patch-clamp remains unmatched in fundamental research due to its versatility. In new work, reported in ("Force-Controlled Patch Clamp of Beating Cardiac Cells"), researchers merged the patch clamp and atomic force microscope (AFM) techniques, thus equipping the patch-clamp with the sensitive AFM force control. This was possible using the FluidFM, a force-controlled nanopipette based on microchanneled AFM cantilevers. First, the compatibility of the system with patch-clamp electronics and its ability to record the activity of voltage-gated ion channels in whole-cell configuration was demonstrated with sodium (NaV1.5) channels. Second, we showed the feasibility of simultaneous recording of membrane current and force development during contraction of isolated cardiomyocytes. Force feedback allowed for a gentle and stable contact between AFM tip and cell membrane enabling serial patch clamping and injection without apparent cell damage. The tool's ability to obtain simultaneous electrophysiological and mechanical information will render it a valuable tool in the field of mechanotransduction. Yet, the enhanced stability and repeatability of the patch clamp protocol sustained by the force feedback are of interest for the entire field of electrophysiology. In addition, the whole process has the potential to be automated, as both the AFM and the pressure controller are fully programmable.