ABSTRACT
INTRODUCTION TO ION CHANNEL STRUCTURE AND FUNCTION Ion channels are defined as proteins forming water-filled pores in cell membranes. Their basic function is to catalyze the movement of ions through the plasma membrane of cells. They are separable from ion transporters by their lack of energy dependence and their high ion conductance rate (often >106 ions/sec) (1). All ion channels limit the permeation of ions based upon the charge and identity of the permeating ions. Structurally, ion channels at their most fundamental level contain two transmembrane (TM) domains joined by a loop comprising part/all of the selectivity filter of the pore. Most ion channels contain 3, 4, or 5 of these basic units to make up a trimer, tetramer, or pentamer, respectively. Up to five additional transmembrane domains can be attached to the two basic TM domains for each subunit. The macromolecular complex most commonly contains six TM domains in a tetramer format for voltage-gated channels, and three TM domains in a pentamer format for ligand-gated channels (Fig. 1). The voltage sensitivity domain (if present) is carried via a series of charged amino acid residues in a minimum of one TM domain. Ligand sensitivity, in contrast, is via ligand binding to a large extracellular region (usually the N-terminus), similar to what is contained in the 7-TM family of G-protein-coupled receptors. Both voltage and ligand activation methods require coupling of the sensor to a gate region near the inner mouth of the channel, which occurs via other parts of the protein. Opening of the gate allows a flow of charged ions to occur down their electrochemical gradient (passively). Subsequent gating or turning off of ion flow occurs in many ion channels and is termed both inactivation (for voltage-gated) and desensitization (for ligand-gated). For more complete descriptions of the structure of ion channels, the reader is referred to reviews for voltage-gated (2-4), for ligand-gated (5,6), and for mechanosensitive ion channels (7).
