Emergence and maintenance of excitability: kinetics over structure

•Excitability entails tuning of both structure and kinetics in a large parameter space.•Controlled protein expression places a cell in a ballpark of excitability class.•Given expressed structure, self-organized kinetic parameters regulate excitability.•Self-organization of kinetic parameters is driven by microscopic fluctuations.•Controlled expression and self-organized kinetics cover a continuum of timescales.

The capacity to generate action potentials in neurons and other excitable cells requires tuning of both ionic channel expression and kinetics in a large parameter space. Alongside studies that extend traditional focus on control-based regulation of structural parameters (channel densities), there is a budding interest in self-organization of kinetic parameters. In this picture, ionic channels are continually forced by activity in-and-out of a pool of states not available for the mechanism of excitability. The process, acting on expressed structure, provides a bed for generation of a spectrum of excitability modes. Driven by microscopic fluctuations over a broad range of temporal scales, self-organization of kinetic parameters enriches the concepts and tools used in the study of development of excitability.