Ion channel engineering for modulation and de novo generation of electrical excitability

Ion channels play essential roles in regulating electrical properties of excitable tissues. By leveraging various ion channel gating mechanisms, scientists have developed a versatile set of genetically encoded tools to modulate intrinsic tissue excitability under different experimental settings. In this article, we will review how ion channels activated by voltage, light, small chemicals, stretch, and temperature have been customized to enable control of tissue excitability both in vitro and in vivo. Advantages and limitations of each of these ion channel-engineering platforms will be discussed and notable applications will be highlighted. Furthermore, we will describe recent progress on de novo generation of excitable tissues via expression of appropriate sets of engineered voltage-gated ion channels and discuss potential therapeutic implications.