Kir3.4 | GIRK4 | Potassium Voltage-Gated Channel Subfamily J Member 5
Family:
Inward-rectifier potassium ion channel
Subgroups:
Seven families channels demonstrate robust inward rectification: Kir1.1; Kir2.1 - Kir2.4; Kir3.1 - Kir3.4, Kir4.1 - Kir4.2; Kir5.1, Kir6.1 - Kir6.2; Kir7.1
Topology:
The channel protein contains two membrane spanning alpha helices denoted as M1 and M2. Four identical subunits form a functional homotetramer, heterotetramers can combine with members of the same subfamily
Kir3.4 Background Information
Kir3.4, also colled GIRK4, is a inward rectifier potassium channel which is a mamber of the subfamily of G protein-coupled inwardly-rectifying potassium channels (GIRKs). In the heart, it forms heteromers with Kir3.1 (GIRK1). When activated by parasympathetic signals such as acetylcholine through M2 muscarinic receptors, it causes an outward current of potassium, which slows down the heart rate. Kir3.4 and Kir3.1 are as well called muscarinic potassium channels and mediate the current IKAChthe heart.
Gene:
KCNJ5
Human Protein:
UniProt P48544
Tissue:
Heart, Islets, exocrine pancreas, liver. Expressed in the adrenal cortex, particularly the zona glomerulosa.
Function/ Application:
ACh-activated K+ current in the heart (IKACh)
Pathology:
Andersen-Tawil syndrome, Long QT syndrome 13 (LQT13), Hyperaldosteronism familial 3 (HALD3), Adrenal hyperplasia, abnormal circulating renin, Autosomal dominant inheritance. Mutated GIRK4 has been found in aldosterone-producing adrenal adenomas and can be responsible for aldosteronism.
Interaction:
Associates with Kir3.1 (GIRK1), Kir3.2 (GIRK2) or Kir3.3 (GIRK3) to form a G-protein activated heteromultimer pore-forming unit. Interacts with Adrenoceptor beta 2, PRKACG, PRKACB, GNG12, Gamma-aminobutyric acid B receptor 1 and 2, Dopamine receptor D4
Modulator:
Tertiapin-Q, Barium chloride, Nicorandil, Minoxidil, Glyburide, 4-AP
Assays:
Patch clamp
Recommended Reviews:
Kubo et al. (2005) International Union of Pharmacology. LIV. Nomenclature and Molecular Relationships of Inwardly Rectifying Potassium Channels. Pharmacol Rev 57(4):509-526