Ion channel selectivity through ion-modulated changes of selectivity filter pKa values
Significance Ion channels that employ carboxylic residues in their selectivity filters (SFs) are found in many realms of life and are important in essential physiological processes. We study bacterial Nav channels which employ four glutamic acid residues in their SF, and we propose a different view of how ion channel selectivity is achieved in nature, based on the difference in pKa values of the SF glutamates in the presence of different ion types. Because of the observed sensitivity of pKa values on the geometry of the SF, this could be important in other channels with carboxylic residues in the SF, e.g., voltage-gated Ca2+ channels, and could possibly explain the large variety in observed selectivities of such channels.