Ion channels are key components in a wide variety of biological processes. The selectivity of ion channels is the key to many biological process. Selectivities in both calcium and sodium channels can be described by the reduced models, taking into consideration of dielectric coefficient and ion particle sizes, as well as their very different primary structure and properties. These self-organized systems will be modeled and analyzed with energetic variational approaches (EnVarA) that were motivated by classical works of Rayleigh and Onsager. The resulting/derived multiphysics-multiscale systems automatically satisfy the Second Laws of Thermodynamics and the basic physics that are involved in the system, such as the microscopic diffusion, the electrostatics and the macroscopic conservation of momentum, as well as the physical boundary conditions. In this talk, I will discuss the some of the related biological, physics, chemistry and mathematical issues arising in this area.