Slow Changes in the Availability of Voltage-gated Ion Channels: Effects on the Dynamics of Excitable Membranes

Excitability stands at the basis of many physiological systems (e.g., neural systems, cardiac cells, hormonereleasing cell clusters). In most cases, the action potential (the excitation event itself) operates on a relatively fast time scale, whereas the system is modulated at time scales that are many orders of magnitude slower. The search for mechanisms to bridge this time gap usually leads to the addition of complex intracellular biochemical modulation pathways and intercellular communication. Recent experiments and theoretical considerations suggest that intrinsic activity-dependent gating mechanisms of voltage-gated ion channels (the molecules of excitability), and in particular slow changes in the availability of the channels for activation, might contribute significantly to long lasting modulations in excitable systems. These modulations are independent of intraand intercellular mechanisms. The present topical review is aimed at summarizing these experimental findings and theoretical considerations.