Application of the one- and two-dimensional Ising models to studies of cooperativity between ion channels

Biophys J. 1993 Jan;64(1):26-35. doi: 10.1016/S0006-3495(93)81337-7.

Abstract

The Ising model of statistical physics provides a framework for studying systems of protomers in which nearest neighbors interact with each other. In this article, the Ising model is applied to the study of cooperative phenomena between ligand-gated ion channels. Expressions for the mean open channel probability, rho o, and the variance, sigma 2, are derived from the grand partition function. In the one-dimensional Ising model, interactions between neighboring open channels give rise to a sigmoidal rho o versus concentration curve and a nonquadratic relationship between sigma 2 and rho o. Positive cooperativity increases the slope at the midpoint of the rho o versus concentration curve, shifts the apparent binding affinity to lower concentrations, and increases the variance for a given rho o. Negative cooperativity has the opposite effects. Strong negative cooperativity results in a bimodal sigma 2 versus rho o curve. The slope of the rho o versus concentration curve increases linearly with the number of binding sites on a protomer, but the sigma 2 versus rho o relationship is independent of the number of ligand binding sites. Thus, the sigma 2 versus rho o curve provides unambiguous information about channel interactions. In the two-dimensional Ising model, rho o and sigma 2 are calculated numerically from a series expansion of the grand partition function appropriate for weak interactions. Virtually all of the features exhibited by the one-dimensional model are qualitatively present in the two-dimensional model. These models are also applicable to voltage-gated ion channels.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Biophysical Phenomena
  • Biophysics
  • Electrochemistry
  • Ion Channel Gating / physiology
  • Ion Channels / chemistry*
  • Ligands
  • Models, Chemical*

Substances

  • Ion Channels
  • Ligands