Abstract

The regulation of neuronal excitability is frequently associated with structural parameters, such as the densities of ion channel proteins. This presentation introduces a complementary mode of regulation—kinetic-based control—in which membrane channel functional availability reflects the history of activation over extended timescales, irrespective of protein synthesis or degradation. This distinction between structure and kinetics challenges conventional models of excitability control, which presume separable system components and predefined targets. In physiological systems, where observables, sensors, and actuators are integrated within the same molecular substrates, conventional decomposition-based approaches fall short. I propose and demonstrate the use of closed-loop methodological designs as a means for studying regulation of excitability under such conditions.