The Role of the Ion Dehydration Process in Low and High Conductance K Channels

Abstract

Potassium channels are known for exhibiting a wide conductance rate from 8.2 pS to 250 pS despite that selectivity filter is largely conserved. Some aspects about the relation between the charge distribution along to the pore and the conductance rate have been studied. In Shaker channel, a low conductance K-channel, one single point mutation of the P475D increases the 4-fold the maximal unitary conductance. At the same time, BK channels, a large conductance K-channel, has been demonstrated that a ring of negative charged residues in the intracellular entrance are key residues in the control of the maximal ion transport rate. Another main difference between low and high conductance K-channels is the size of the channel pore, BK has a much wider internal vestibule than Shaker. In order to understand at the molecular level the conduction process in both K+ channel classes, we performed molecular dynamics simulations using an applied external electric field to compare the structural properties of BK and Shaker channels (+300 mV, +600 mV and +800mV). Different ranges of currents were observed in Shaker and BK under the influence of the external electric field. At all the voltages tested, BK present the largest rate of ion translocation. Interestingly, K+ ions moving from the intracellular side up to the S4 site show a dehydration pattern, which is more efficient in BK channels. Other channel structural properties are discussed in the context of the dehydration process of the K ions in Shaker and BK.Acknowledgements: CINV is a Millennium Institute. R.S thanks CONICYT doctoral fellowship and project FONDECYT 1110430 (RL), 1131003 (FGN), 1120819 (DN) and proyecto Anillo ACT1107 (FGN)