THE MODULATORY SITE FOR THE ACTION OF GADOLINIUM ON SURFACE-CHARGES AND CHANNEL GATING

The gadolinium (Gd3+)-induced shift of potential dependence and modula ted gating of Na and K channels were analyzed. In a previous investiga tion, we explained the shift in terms of pure screening (no binding) o f fixed surface charges and the modulation by binding to modulatory si tes on the channels. In the present paper, we have extended this model by including effects on the charge density of Gd3+ binding to the mod ulatory sites. From fitting the extended model to experimental data, t he charge density was estimated to be -0.6 e nm(-2), and the Gd3+-indu ced charge change to be +0.15 e nm(-2), and the maximal scaling factor to be 7.5 for both Na and K channels. Intrinsic K-D values for bindin g to the K and Na channels were estimated to be 140 and 380 mM, respec tively. Estimations of the extracellular charge density, from primary structures of cloned channels, were found to be in agreement with esti mations based on the present model. The modulatory site was suggested to be located at the cluster of negatively charged residues between th e fifth transmembrane segment (S5) and the pore-forming region for bot h Na and K channels. These suggestions imply several testable predicti ons about different K channels.