Structural predictions of HCN/CNG ion channels: Insights on channels' gating

Evolution built a membrane around the earliest forms of life in order to isolate them from the external environment. The cell membrane is constituted by two layers of phospholipids, which are molecules having a polar head and non-polar tails. Two films of these molecules are assembled together by hydrophobic forces building a very stable lipid bilayer. Inserted in this amphiphilic environments are membrane proteins, which have both hydrophobic and hydrophilic regions on their surface. In highly evolved and specified cells this class of proteins carries out a variety of different activities essential for the cell and organism life, like the antibody recognition in lymphocytes and the nervous pulse transmission in neurons. Although the presence of the membrane helps cells to retain vital ingredients, it prevents the access to necessary ionized substrates and ions, because the hydrophobic core is a high free energy barrier in the diffusion of charged molecules. Membrane spanning pores are a common feature to ionic channels (Hille, 2001;Chang et al., 1998), and they are presents in different classes of other biological transporter proteins like bacterial porins and aquaporins. Special membrane proteins, the ionic channels, form holes through the cell membrane, providing a feasible path for ion exchanges.