Ion ChannelsMediators of ion currents across cell membranes
Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia USA
Ion channels comprise a large class of highly specialized intrinsic membrane proteins that mediate the flow of ions down their electrochemical gradients across cell membranes. As such they are responsible for membrane excitability in nerve, muscle and other cell types. Ion channels contain a hydrophilic pore through which ions can... read moreflow, imbedded within a hydrophobic region that interacts with the lipid bilayer membrane.
Two fundamental properties of ion channels are selectivity and gating. Most ion channels are selective, in that their pores are permeant to a particular ion but not others. Accordingly ion channels are often named for the ion they allow to flow (sodium channels, potassium channels, calcium channels, chloride channels). Channels may exist in an open conformation or state, through which ions are able to flow, and a closed state which does not permit ion flow. The switch between these states, often referred to as channel gating, can be regulated by the membrane voltage (voltage-gated channels), the binding of an extracellular ligand such as a neurotransmitter or hormone (ligand-gated channels), or the binding of an intracellular signaling molecule such as ATP, a cyclic nucleotide or calcium ion. Protein structure determination using X-ray crystallography has brought our understanding of permeation and selectivity in ion channels to atomic resolution, and exquisitely sensitive biophysical techniques can be used to study gating at the level of individual ion channel protein molecules.
A large number of human disorders, including for example some forms of deafness and epilepsy, and certain cardiac abnormalities, can be attributed to defects in one or another kind of ion channel. Accordingly ion channels are important targets in drug discovery efforts to alleviate these disorders.