Ionic Channels
Abstract
The chapter provides an overview of passive and active ionic channels (intrinsic transmembrane proteins that span the membrane), which regulate the movements of ions into and out of biological cells and in the membrane-bound organelles; their role is central to the life of the cells, as the single genetic abnormalities that cause over 600 human diseases have now been identified, including a variety of channelopathies. In the introductory part, the remarkable diversity of ionic channels is classified according to functional characteristics (electrophysiologic behavior, inhibition or stimulation by pharmacologic agents, activation by extracellular agonists, and modulation by intracellular messengers) or structural characteristics (amino acid sequence homology and the kinds of subunits of which they are composed). In the second part, the biophysical transport of ions through biological membranes is considered as an interplay between (gated) active membrane transport (which explains the origin of different ion concentrations from the inside and outside of the cell membrane) and (nongated) passive membrane transport (explaining the resting potential of the membrane, as a consequence of the concentration gradient established by active transport). In the last part, we summarize the major structural features of the known 18 distinct families of ionic channels that have been identified in mammals by cloning of their pore-forming subunits, where the hypothetical membrane topologies are based primarily on hydropathy analysis; when annotation of the human genome is completed, it will eventually be possible to provide a definitive survey of channel types and functions.