Current and selectivity in a model sodium channel under physiological conditions: Dynamic Monte Carlo simulations

A reduced model of a sodium channel is analyzed using Dynamic Monte Carlo simulations. These include the first simulations of ionic current under approximately physiological ionic conditions through a model sodium channel and an analysis of how mutations of the sodium channel's DEKA selectivity filter motif transform the channel from being Na+ selective to being Ca2+ selective. Even though the model of the pore, amino acids, and permeant ions is simplified, the model reproduces the fundamental properties of a sodium channel (e.g., 10 to 1 Na+ over K+ selectivity, Ca2+ exclusion, and Ca2+ selectivity after several point mutations). In this model pore, ions move through the pore one at a time by simple diffusion and Na+ versus K+ selectivity is due to both the larger K+ not fitting well into the selectivity filter that contains amino acid terminal groups and K+ moving more slowly (compared to Na+) when it is in the selectivity filter. (C) 2011 Elsevier B.V. All rights reserved.