Homeostasis, failure of homeostasis and degenerate ion channel regulation

Most neurons express a wide variety of ion channels with diverse properties, providing a rich toolbox for tuning neural function. Coexpressed channel types are often degenerate: they share overlapping roles in shaping electrophysiological properties. This can allow one set of channels to compensate the role of others, thus making nervous systems robust to perturbations such as channel deletions and mutations, expression noise or environmental disturbances. In tandem, activity-dependent homeostatic mechanisms can actively regulate channel expression to counteract perturbations by sensing changes in physiological activity. However, recent work shows that in spite of degeneracy and homeostatic regulation, the compensatory outcome of a perturbation can be unpredictable. Sometimes a single mutation in an ion channel gene can be catastrophic, while in other contexts a similar loss of function might be compensated. Compensation sometimes fails even when there may be many potential ways to compensate using available channels. Theoretical models show how homeostatic mechanisms that regulate degenerate conductances can fail and even cause pathologies through aberrant compensation