Correlations in ion channel expression emerge from homeostatic tuning rules

Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):E2645-54. doi: 10.1073/pnas.1309966110. Epub 2013 Jun 24.

Abstract

Experimental observations reveal that the expression levels of different ion channels vary across neurons of a defined type, even when these neurons exhibit stereotyped electrical properties. However, there are robust correlations between different ion channel expression levels, although the mechanisms that determine these correlations are unknown. Using generic model neurons, we show that correlated conductance expression can emerge from simple homeostatic control mechanisms that couple expression rates of individual conductances to cellular readouts of activity. The correlations depend on the relative rates of expression of different conductances. Thus, variability is consistent with homeostatic regulation and the structure of this variability reveals quantitative relations between regulation dynamics of different conductances. Furthermore, we show that homeostatic regulation is remarkably insensitive to the details that couple the regulation of a given conductance to overall neuronal activity because of degeneracy in the function of multiple conductances and can be robust to "antihomeostatic" regulation of a subset of conductances expressed in a cell.

Keywords: computational models; control theory; neuronal excitability; robustness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Homeostasis*
  • Ion Channels / metabolism*
  • Models, Biological
  • Neurons / physiology

Substances

  • Ion Channels