Ion channels have two main signalling functions: either they can generate second messengers or they can function as effectors by responding to such messengers. Their role in signal generation is mainly centred on the Ca2+ signalling pathway, which has a large number of Ca2+ entry channels and internal Ca2+ release channels, both of which contribute to the generation of Ca2+ signals.
Ion channels are also important effectors in that they mediate the action of different intracellular signalling pathways. There are a large number of K+ channels and many of these function in different aspects of cell signalling. The voltage-dependent K+ (KV) channels regulate membrane potential and excitability. The inward rectifier K+ (Kir) channel family has a number of important groups of channels such as the G protein-gated inward rectifier K+ (GIRK) channels and the ATP-sensitive K+ (KATP) channels. The two-pore domain K+ (K2P) channels are responsible for the large background K+ current. Some of the actions of Ca2+ are carried out by Ca2+-sensitive K+ channels and Ca2+-sensitive Cl− channels. The latter are members of a large group of chloride channels and transporters with multiple functions.
There is a large family of ATP-binding cassette (ABC) transporters some of which have a signalling role in that they extrude signalling components from the cell. One of the ABC transporters is the cystic fibrosis transmembrane conductance regulator (CFTR) that conducts anions (Cl− and HCO3−) and contributes to the osmotic gradient for the parallel flow of water in various transporting epithelia. Many of these epithelia also express aquaporins, which are water channels that increase the flux of water during fluid secretion or absorption. The cation channel of sperm (CatSper) is sensitive to intracellular pH and has a vital role to play in maintaining sperm hyperactivity prior to fertilization. Finally, there are hyperpolarizing-activated cyclic nucleotide-gated (HCN) channels that play an important role in various pacemaker mechanisms both in the heart and nervous system.
Hemichannels provide membrane channels responsible for releasing ions and messengers from cells. On the other hand, gap junctions provide an intercellular pathway to transfer ions and messengers between cells.
Mechanosensitive channels that open in response to membrane deformation have multiple functions especially in sensory systems such as touch and hair cell mechanoelectrical transduction.
A large number of genetic diseases have been traced to mutations in various channels. For example, mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) channel is the cause of cystic fibrosis. Many of the other channelopathies have been linked to changes in the channels that gate either the entry or the release of Ca2+.
- © 2014 Portland Press Limited