Ion Accumulation in a Biological Calcium Channel:  Effects of Solvent and Confining Pressure

Abstract

Biological L-type calcium channels selectively accumulate Ca 2+ , even when there is 10 5 more Na + in the surrounding electrolyte solution. Like other Ca 2+ -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 Ca 2+ signal transducer able to perform substantial mechanical work in a Ca 2+ regulated protein.

Computational Methods for Biomolecular Electrostatics

“…In particular, implicit solvent methods are only capable of describing non-specific interactions between solvent and solute. In general, explicit solvent methods should be used wherever the detailed interactions between solvent and solute are important, such as solvent finite size effects in ion channels (Nonner et al, 2001), strong solvent-solute interactions (Bhattacharrya et al, 2003), strong solvent coordination of ionic species (Figueirido et al, 1994;Yu et al, 2004), and saturation of solvent polarization near a membrane (Lin J.-H. et al, 2002). Similarly, as mentioned earlier in the context of RNA-ion interactions, implicit descriptions of mobile ions can also become questionable in some cases, such as high ion valency or strong solvent coordination, specific ion-solute interactions, and high local ion densities (Holm et al, 2001), where the ions interact with each other or with the solute directly.…”

Ionic Coulomb blockade and anomalous mole fraction effect in the NaChBac bacterial ion channel and its charge-varied mutants

“…In equilibrium, the chemical potentials in the bulk m b and in the channels m c are equal, m b = m c [25,26]:…”

Designing biomimetic pores based on carbon nanotubes

“…ELIC, a bacterial pentemeric ligand-gated ion channel, is cation selective and has a ring of five anionic glutamate (E) side chains (9). Rings of anionic side chains have also been suggested to play a key role in the ion selectivity of voltagegated calcium (Cav) and sodium (Nav) channels (10)(11)(12). Thus, Cav (and some Nav) channels have four anionic residues in a ring (an EEEE motif, where E is the amino acid glutamate).…”