Ion accumulation in a biological calcium channel: Effects of solvent and confining pressure

Biological L-type calcium channels selectively accumulate Ca2+, even when there is 10(5) more Na+ in the surrounding electrolyte solution. Like other Ca2+-chelating molecules, the L-type calcium channel has four carboxylate groups that contain eight oxygen ions. In this modeling study, these oxygens are confined to a small subvolume of the channel protein (the "filter") that is embedded in a bulk electrolyte solution (the "bath"). With the system in equilibrium, the concentrations of the ions and water in the filter are computed, given their concentrations in the bath. The excess thermodynamic properties are calculated using the mean spherical approximation (MSA), with water modeled as an uncharged hard sphere [the so-called solvent primitive model (SPM)] and a dielectric coefficient. Use of the SPM is an extension of previous work, where water was modeled as an amorphous dielectric, Other new aspects included in this study are changing the volume of the filter in response to the pressure generated by the water and ions in the filter and modeling solvation effects in more detail. The model is calibrated with a single experimental measurement. Predictions are compared to experimental results, where available, and future experiments are suggested. Finally, the model is considered as a Ca2+ signal transducer able to perform substantial mechanical work in a Ca2+ regulated protein.