  Ion channels are specific proteins present in the membranes of living cells.
They control the flow of specific ions through a cell, initiated by an ion
channel's electrochemical gradient. In doing so, they control important
physiological processes such as muscle contraction and neuronal connectivity,
which cannot be properly activated if these channels go haywire, leading to
life-threatening diseases and psychological disorders. Here, we will develop a
generalized microscopic theory of ion selectivity applicable to KcsA, Na$_{\rm
v}$Rh and Ca$_{\rm v}$ (L-type) ion channels. We unambiguously expose why and
how a given ion-channel can be highly selective, and yet has a conductance of
the order of one million ions per second, or higher. We will identify and prove
the correct physico-biochemical mechanisms that are responsible for the high
selectivity of a particular ion in a given ion channel. The above mechanisms
consist of five conditions, which can be directly associated to these
parameters - (i) dehydration energy, (ii) concentration of the "correct" ions
(iii) Coulomb-van-der-Waals attraction, (iv) pore and ionic sizes, and
indirectly to (v) the thermodynamic stability and (vi) the "knock-on" assisted
permeation.
