Na⁺/Ca²⁺selectivity in the bacterial voltage-gated sodium channel NavAb

The recent publication of a number of high resolution bacterial voltage-gated sodium channel structures has opened the door for the mechanisms employed by these channels to distinguish between ions to be elucidated. The way these channels select between Na⁺ and K⁺ has been investigated in computational studies, but the selectivity for Na+ over Ca2⁺ has not yet been studied in this way. Here we use molecular dynamics simulations to calculate the energetics of Na⁺ and Ca2⁺ transport through the channel. Single ion profiles show that Ca2⁺ experiences a large barrier midway through the selectivity filter that is not seen by Na⁺. This barrier is caused by the need for Ca2⁺ to partly dehydrate to pass through this region and the lack of compensating interactions with the protein.Multi-ion profiles show that ions can pass each other in the channel, which is why the presence of Ca2⁺ does not block Na⁺ conduction despite binding more strongly in the pore.