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

摘要

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.