Synthetic Electrophysiology

Most research in electrophysiology focuses on identifying the roles of component ion channels in governing the electrical dynamics of complex tissues such as heart or brain. We are exploring a synthetic approach: starting with electrically inert cells, what collective behaviors emerge as we introduce specific ion channels, one at a time? We find that even with simple combinations of ion channels, surprisingly rich and complex dynamics can emerge. In HEK293 cells expressing an inward-rectifier potassium channel, K ir 2.1, electrical polarization occurs via a stepwise jump. In a confluent monolayer of these cells, electrical polarization spreads via collective bioelectric domain wall. Simple numerical simulations reproduce these effects. Cells expressing K ir 2.1 and a voltage-gated sodium channel, Na V 1.5, produce action potential-like spikes. When these cells are grown into a confluent monolayer, the spikes propagate as collective waves. We use patterned optogenetic stimulation to excite these cells, and wide-field voltage imaging to map the voltage dynamics. Cells grown on different-shaped islands show geometry-dependent transitions from regular beating, to period doubling, to arrhythmia. These experiments illustrate how qualitatively new and surprising phenomena can emerge from the many-body behavior of electrically coupled cells, even when the electrophysiology of the individual cells is understood exhaustively