Kir3.4 channels
| Channel name | Kir3.4 |
| Description | G-protein gated, inwardly rectifying potassium channel Kir3.4 subunit |
| Other names | GIRK4 |
| Molecular information | Human (KCNJ5): 419aa, Locus ID: 3762, GenBank: L47208, NM_000890, PMID: 8558261,1 chr. 11q24 |
| Rat (Kcnj5): 419aa, Locus ID: 29713, GenBank: L35771, NM_017297, PMID: 7877685,2 chr. 8q21 | |
| Mouse (Kcnj5): 419aa, Locus ID: 16521, GenBank: U33631, NM_010605, PMID: 7499385,3 chr. 11q23 | |
| Associated subunits | Kir3.1, Kir3.2, Kir3.3, Kir3.54 |
| Functional assays | Voltage-clamp |
| Current | IGIRK |
| Conductance | 35pS (in symmetrical 140 mM K+) |
| Ion selectivity | Highly K+-selective |
| Activation | Gβγ subunits at 1 to 50 nM |
| Inactivation | Voltage- and RGS protein-dependent |
| Activators | Kir3.4 and Kir3.4-containing GIRK channels are activated by direct binding to the Gβγ subunits of PTX-sensitive G proteins; modified by PIP2, sodium |
| Gating inhibitors | Gα subunits (by binding Gβγ subunits) |
| Blockers | Nonselective: Ba2+, Cs+, tetraethylammonium, 4-aminopyridine |
| Radioligands | None |
| Channel distribution | Heart atria and other pacemaking tissues, ventricles in human; restricted areas of the brain: islands of Calleja, cerebellum, habenula, cortex, hippocampal pyramidal cells, less in skeletal muscle, urinary bladder, lungs, eyes; for a distribution in rat brain see ref. 5 |
| Physiological functions | Mediates vagal-induced slowing of heart rate by muscarinic acetylcholine M2 and Gαi-coupled adenosine and somatostatin receptors; in brain, possibly activated by muscarinic acetylcholine, GABAB, dopamine D2, 5-HT1A, adenosine, somatostatin, and enkephalin receptors and β2-adrenoceptors |
| Mutations and pathophysiology | Not established |
| Pharmacological significance | Atropine blocks M2 receptor-mediated activation in heart; adenosine activation is used in the treatment of supraventricular tachycardias |
| Comments | The Xenopus homolog (U42207) of mammalian Kir3.4 has been given the nomenclature Kir3.54 |
aa, amino acids; chr., chromosome; PTX, picrotoxin; 5-HT, 5-hydroxytryptamine.
↵1. Spauschus A, Lentes KU, Wischmeyer E, Dissmann E, Karschin C, and Karschin A (1996) A G protein-activated inwardly rectifying K+ channel GIRK4 from human hippocampus associates with other GIRK channels. J Neurosci 16:930-942
↵2. Krapivinsky G, Gordon E, Wickman K, Velimirovic B, Krapivinsky L, and Clapham DE (1995) The G protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K+ channel proteins. Nature (Lond) 374:135-141
↵3. Lesage F, Guillemare E, Fink M, Duprat F, Heurteaux C, Fosset M, Romey G, Barhamin J, and Lazdunski M (1995) Molecular properties of neuronal G-protein-activated inwardly rectifying K+ channels. J Biol Chem 270:28660-28667
↵4. Hedin K, Lim N, and Clapham D E (1996) Cloning of Xenopus laevis inwardly rectifying K+ channel subunit that permits GIRK1 expression of IKACh currents in oocytes. Neuron 16: 423-429
↵5. Murer G, Adelbrecht C, Lauritzen I, Lesage F, Lazdunski M, Agid Y, and Raisman-Vozari R (1997) An immunocytochemical study on the distribution of two G-protein-gated inward rectifier potassium channels(GIRK2 and GIRK4) in the adult rat brain. Neuroscience 80:345-357