On the selectivity of KcsA potassium channel: asymptotic analysis and computation

Abstract: Potassium (K$^+$) channels regulate the flux of K$^+$ ions through cell membranes and plays significant roles in many physiological functions. This work studies the KcsA potassium channel, including the selectivity and current-voltage (IV) relations. A modified Poisson-Nernst-Planck system is employed, which include the size effect by Bikerman model and solvation energy by Born model. The selectivity of KcsA for various ions (K$^+$, Na$^+$, Cl$^-$, Ca$^{2+}$ and Ba$^{2+}$) is studied analytically, and the profiles of concentrations and electric potential are provided. The selectivity is mainly influenced by permanent negative charges in filter of channel and the ion sizes. K$^+$ is always selected compared with Na$^+$ (or Cl$^-$), as smaller ion size of Na$^+$ causes larger solvation energy. There is a transition for selectivity among K$^+$ and divalent ions (Ca$^{2+}$ and Ba$^{2+}$), when negative charge in filter exceeds a critical value determined by ion size. This explains why divalent ions can block the KcsA channel. The profiles and IV relations are studied by analytical, numerical and hybrid methods, and are cross-validated. The results show the selectivity of the channel and also the saturation of IV curve. A simple strategy is given to compute IV relations analytically, as first approximation. The numerical method deals with general structure or parameters, but the limitations and difficulties of pure numerical simulation are also pointed out. The hybrid method provides IV relations most effectively for comparison. The reason for saturation of IV relation is illustrated, and the IV curve shows agreement with the profile and scale of experimental results.