Protein Domain : Potassium channel, inwardly rectifying, Kir3.4 IPR003277

Type	Family
Description	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 [ ]. 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 [, ].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 [ ].The Kir3.x channel family is gated by G-proteins following G-protein coupled receptor (GPCR) activation. They are widely distributed inneuronal, atrial, and endocrine tissues and play key roles in generating late inhibitory postsynaptic potentials, slowing the heart rate andmodulating hormone release. They are directly activated by G-protein beta-gamma subunits released from G-protein heterotrimers of the G(i/o)family upon appropriate receptor stimulation.Kir3.4 is thought to associate with Kir3.1, to form hetero-tetrameric acetylcholine-activated K+ channels, in the heart. Their activation,following stimulation of the vagus nerve, leads to slowing of the heart, and reduction in contractile force. In the brain, Kir3.4 distribution hasbeen found to be quite restricted, being found in some neuronal populations, such as Purkinje cells and neurones of the globus pallidus and the ventralpallidum [ ]. A recent study has suggested that Kir3.4 may confer mechano-sensitive properties on Kir channels, since channels containing it areinactivated by membrane stretch forces [ ].Mutations of the Kir3.4 gene have been linked to Long QT syndrome 13 (LQT13) [ ] and Hyperaldosteronism, familial, 3 (HALD3) [].
Short Name	K_chnl_inward-rec_Kir3.4