Modulation of ion channels in neurons and other cells

The field of ion channel modulation has entered a stage of maturity. The development of powerful new molecular biological and biophysical approaches has provided important new insights into the structure and function of ion channels and has revealed them as dynamic entities whose activity can be regulated. The physiological consequences of such regulation are obvious for so-called excitable cells like nerve and muscle cells, but it is also evident that modulation occurs in many other cell types, where its effects on the lifestyle of the cell are less clear. Furthermore, the number of ion channels that have been shown to be subject to modulation continues to increase, and the end is not yet in sight. For example, exciting information is beginning to emerge about gating and conduction properties of the large class of channels coupled to excitatory amino acid receptors (Mayer 1987), but their modulation has not yet been studied in any detail. In any event, there no longer is any doubt that modulatability is an intrinsic property of many and perhaps all membrane ion channels. The mechanisms of channel modulation are also turning out to be more diverse than was first suspected. One possible explanation for this diversity is to provide a broad temporal spectrum for the regulation of channel activity. One temporal extreme may be a directly coupled system such as the nicotinic acetylcholine receptor/channel, where interactions between the several subunits of a single macromolecular complex determine rapid channel gating. The other extreme may be covalent modification (by protein phosphorylation or other covalent change), which results in a functional change that can long outlast the initial stimulus. G-protein modulation, which involves the (presumably) noncovalent interaction between distinct membrane proteins, may provide for intermediate duration changes in channel properties. Whether these mechanisms will be joined by others that provide for an even more subtle temporal discrimination is an exciting question for the future.