Tuning Ca²⁺ Permeation in Cyclic Nucleotide–gated Channels

Most ion channels consist of several different subunits, and figuring out the exact role that each subunit polypeptide plays in channel regulation is a daunting and rewarding task. The challenge is to find out (a) which subunits coassemble to form the native channel protein, (b) how many copies of each individual polypeptide are contained in the channel, (c) which subunits contribute to the lining of the conducting pore and which just stick to the internal or external face of the channel, and (d) which of the subunits are neighbors in the native channel. The reward has two equally exciting aspects: the studies can yield glimpses into the mechanisms for fine tuning nearly all functional parameters, including ion selectivity, regulation of open probability (gating), and channel expression. In addition, a modular system of channel assembly may become apparent in which a cell chooses from a repertoire of subunits to build...