Until recently, the two essential aspects of channel function seemed to be clearly distinct: a selectivity filter that discriminates among incoming ions and an intracellular gate that regulates the ion flux. As usual, reality is more complex, and this traditional view of ion channels is changing rapidly. Although a physical gate appears to operate at the intracellular part of the channel and undergo conformational transitions associated with the open-closed transitions of the channels, there is much more going on in the permeation pathway than was initially appreciated and the notion of a fairly “passive” or “rigid” selectivity filter is no longer adequate. Initial observations that different permeant ions could alter channel gating and/or inactivation rates pointed in that direction, but new data provides a compelling demonstration for an extended and more complex function of the pore, beyond its role in selectivity.
Several pieces of evidence,...
