K+ Conduction in the Selectivity Filter of Potassium Channels Is Monitored by the Charge Distribution along Their Sequence

AbstractPotassium channels display a high conservation of sequence of the selectivity filter (SF), yet nature has designed a variety of channels that present a wide range of absolute rates of K+ permeation. In KcsA, the structural archetype for K channels, under physiological concentrations, two K+ ions reside in the SF in configurations 1,3 (up state) and 2,4 (down state) and ion conduction is believed to follow a throughput cycle involving a transition between these states. Using free-energy calculations of KcsA, Kv1.2, and mutant channels, we show that this transition is characterized by a channel-dependent energy barrier. This barrier is strongly influenced by the charges partitioned along the sequence of each channel. These results unveil therefore how, for similar structures of the SF, the rate of K+ turnover may be fine-tuned within the family of potassium channels