Using a diamond heater-thermometer to thermally modulate ion channels, trigger action potentials and induce calcium release in living cells

Even though temperature is a crucial physical parameter for living systems, it is mostly regarded in physiology as a factor contributing to the whole-body temperature of multicellular organisms. Moreover, the lack of suitable instrumentation has made temperature control at the single-cell level challenging, slow and unreliable. Here, we aim at breaking that limit by utilizing a recently-developed Diamond Heater-Thermometer (DHT) technique for non-invasive controllable thermal stimulation of individual living cells and their compartments using a single engineered diamond particle attached to a glass capillary. In particular, we demonstrate applications of the DHT technique for the intracellular release of free calcium in HeLa cells, as well as fast reproducible thermal modulation of ionic current in voltagegated Nav1.5 sodium channels in HEK293 cells. Additionally, we show a robust modulation of the cardiac action potential on freshly isolated murine adult ventricular cardiomyocytes and fast thermal excitation of action potential in primary neurons. The DHT approach of manipulating ultra-local intracellular temperatures down to the nanoscale has the potential to uncover previously inaccessible effects in various intracellular processes related to the endogenous nanoscale heat sources (e.g., heat release in the open ion channels, ionic pumps, uncoupled mitochondria, local calcium release processes). Moreover, thanks to the plug-and-play configuration of the demonstrated fiber-coupled Diamond Heater-Thermometer, its ease-of-use and versatility, such a technique can become part of a standard toolbox for electrophysiology, calcium imaging, and experimental life sciences in general.