Pathways & interactions
Potassium channel, inwardly rectifying, Kir (IPR016449)
Short name: K_chnl_inward-rec_Kir
Overlapping homologous superfamilies
- Potassium channel, inwardly rectifying, Kir, cytoplasmic (IPR013518)
- Immunoglobulin E-set (IPR014756)
- Potassium channel, inwardly rectifying, Kir (IPR016449)
- Inward rectifier potassium channel 13 (IPR008062)
- Potassium channel, inwardly rectifying, Kir1.1 (IPR003268)
- Potassium channel, inwardly rectifying, Kir1.2 (IPR003269)
- Potassium channel, inwardly rectifying, Kir1.3 (IPR003270)
- Potassium channel, inwardly rectifying, Kir2.1 (IPR003271)
- Potassium channel, inwardly rectifying, Kir2.2 (IPR003272)
- Potassium channel, inwardly rectifying, Kir2.3 (IPR003273)
- Potassium channel, inwardly rectifying, Kir3.1 (IPR003274)
- Potassium channel, inwardly rectifying, Kir3.2 (IPR003275)
- Potassium channel, inwardly rectifying, Kir3.3 (IPR003276)
- Potassium channel, inwardly rectifying, Kir3.4 (IPR003277)
- Potassium channel, inwardly rectifying, Kir5 (IPR008061)
- Potassium channel, inwardly rectifying, Kir6.1 (IPR003278)
- Potassium channel, inwardly rectifying, Kir6.2 (IPR003279)
Potassium channels are the most diverse group of the ion channel family [PMID: 1772658, PMID: 1879548]. They are important in shaping the action potential, and in neuronal excitability and plasticity [PMID: 2451788]. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups [PMID: 2555158]: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.
These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+ channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers [PMID: 2448635]. In eukaryotic cells, K+ channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes [PMID: 1373731]. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [PMID: 11178249].
All K+ channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+ selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+ across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+ channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+ channels; and three types of calcium (Ca)-activated K+ channels (BK, IK and SK) [PMID: 11178249]. The 2TM domain family comprises inward-rectifying K+ channels. In addition, there are K+ channel alpha-subunits that possess two P-domains. These are usually highly regulated K+ selective leak channels.
Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release [PMID: 10102275]. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [PMID: 7580148, PMID: 10449331].
Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [PMID: 10102275].