Kir3.4 | GIRK4 | Potassium Voltage-Gated Channel Subfamily J Member 5

K_ir3.4, 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 K_ir3.1 (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. K_ir3.4 and K_ir3.1 are as well called muscarinic potassium channels and mediate the current I_KAChthe 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 (I_KACh)

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 K_ir3.1 (GIRK1), K_ir3.2 (GIRK2) or K_ir3.3 (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