Investigating The Ion Permeation Pathway Of Nav1.5 Ion Channel

The Nav1.5 Voltage Gated Sodium Channels (VGSCs) is one of the most important cation ion channels in humans. Nav1.5 is responsible for initiating the myocardial action potential and blocking Nav1.5 through either mutations or... [ view full abstract ]

The Nav1.5 Voltage Gated Sodium Channels (VGSCs) is one of the most important cation ion channels in humans. Nav1.5 is responsible for initiating the myocardial action potential and blocking Nav1.5 through either mutations or its interactions with small molecule drugs or toxins have been associated with a wide range of cardiac diseases. Investigating the atomic details of the ionic permeation through Nav1.5 is of paramount importance for the electrophysiology and the pathophysiology communities. In the current study, a structural model of Nav1.5 was generated and relaxed by long molecular dynamics simulation. The model was validated against known mutations and also for its ranking power for wide range of Nav1.5 blockers. Of particular interest was the capability of the model to selectively allow sodium ion to pass through the channel’s pore under the influence of the deep electrostatic potential well created by a cluster of negatively charged residues, such as Glu and Asp residue. We believe that data presented within this study will provide an invaluable insight for researchers who are interested in studying the physiology as well as the pathophysiology of Nav1.5.