Na ⁺/Ca ²⁺ selectivity in the bacterial voltage-gated sodium channel NavAb

Abstract

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 Ca ²⁺ has not yet been studied in this way. Here we use molecular dynamics simulations to calculate the energetics of Na ⁺ and Ca ²⁺ transport through the channel. Single ion profiles show that Ca ²⁺ experiences a large barrier midway through the selectivity filter that is not seen by Na ⁺ . This barrier is caused by the need for Ca ²⁺ 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 Ca ²⁺ does not block Na ⁺ conduction despite binding more strongly in the pore.