The G protein-coupled inwardly-rectifying potassium channels (GIRKs) are a family of inward-rectifier potassium ion channel

Inward-rectifier potassium ion channel

Inwardly rectifying potassium channels are a specific subset of potassium selective ion channels. To date, seven subfamilies have been identified in various mammalian cell types...

s which are activated (opened) via a signal transduction

Signal transduction

Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...

 cascade starting with ligand

Ligand (biochemistry)

In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...

-stimulated G protein-coupled receptor

G protein-coupled receptor

G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

s (GPCRs). GPCRs in turn release activated G-protein

G protein

G proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...

 βγ- subunits (G_βγ) from inactive heterotrimeric G protein

Heterotrimeric G protein

"G protein" usually refers to the membrane-associated heterotrimeric G proteins, sometimes referred to as the "large" G proteins. These proteins are activated by G protein-coupled receptors and are made up of alpha , beta and gamma subunits, the latter two referred to as the beta-gamma...

 complexes (G_αβγ). Finally, the G_βγ dimeric protein interacts with GIRK channels to open them so that they become permeable to potassium ions, resulting in hyperpolarization of the cell. G protein-coupled inwardly-rectifying potassium channels are a type of G protein-gated ion channels because of this direct activation of GIRK channels by G protein subunits.

GIRK1 to GIRK3 are distributed broadly in the central nervous system, where their distributions overlap. GIRK4, instead, is found primarily in the heart.

Subtypes

protein	gene	aliases
GIRK1 KCNJ3 Potassium inwardly-rectifying channel, subfamily J, member 3, also known as KCNJ3 or Kir3.1, is a human gene.-See also:* G protein-coupled inwardly-rectifying potassium channel* Inward-rectifier potassium ion channel- External links :...		Kir3.1
GIRK2 KCNJ6 G protein-activated inward rectifier potassium channel 2 is a protein that in humans is encoded by the KCNJ6 gene.-Interactions:KCNJ6 has been shown to interact with KCNJ9 and DLG1.-See also:* G protein-coupled inwardly-rectifying potassium channel...		Kir3.2
GIRK3 KCNJ9 G protein-activated inward rectifier potassium channel 3 is a protein that in humans is encoded by the KCNJ9 gene.-See also:* G protein-coupled inwardly-rectifying potassium channel* Inward-rectifier potassium ion channel...		Kir3.3
GIRK4 KCNJ5 G protein-activated inward rectifier potassium channel 4 is a protein that in humans is encoded by the KCNJ5 gene and is a type of G protein-gated ion channel.-See also:* G protein-coupled inwardly-rectifying potassium channel...		Kir3.4

Examples

A wide variety of G-protein coupled receptors activate GIRKs, including the M₂-muscarinic

Muscarinic acetylcholine receptor M2

The muscarinic acetylcholine receptor M2, also known as the cholinergic receptor, muscarinic 2, is a muscarinic acetylcholine receptor.-Heart:...

, A₁-adenosine, α₂-adrenergic

Alpha-2 adrenergic receptor

The alpha-2 adrenergic receptor is a G protein-coupled receptor associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well...

, D₂-dopamine

Dopamine receptor D2

Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...

, μ-

Mu Opioid receptor

The μ-opioid receptors are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. They are also referred to as μ opioid peptide receptors. The prototypical μ receptor agonist is the opium alkaloid morphine; μ refers to morphine...

 δ-

Delta Opioid receptor

The δ-opioid receptors, also known as delta opioid receptor or simply delta receptor, abbreviated DOR, is an opioid receptor that has enkephalins as its endogenous ligands.-Function:...

, and κ-

Kappa Opioid receptor

The κ-opioid receptor is a protein that in humans is encoded by the OPRK1 gene. The κ-opioid receptor is one of five related receptors that bind opium-like compounds in the brain and are responsible for mediating the effects of these compounds...

opioid

Opioid receptor

Opioid receptors are a group of G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin receptors...

, 5-HT_1A serotonin

5-HT1A receptor

The 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...

, somatostatin

Somatostatin receptor

There are five known somatostatin receptors:* SST1 * SST2 * SST3 * SST4 * SST5 All are G protein-coupled seven transmembrane receptors.-External links:...

, galanin

Galanin receptor

The galanin receptor is a G protein-coupled receptor, or metabotropic receptor which binds galanin.Galanin receptors can be found throughout the peripheral and central nervous systems and the endocrine system. So far three subtypes are known to exist: GAL-R1, GAL-R2, and GAL-R3...

, m-Glu

Metabotropic glutamate receptor

The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs...

, GABA_B, and sphingosine-1-phosphate

Lysophospholipid receptor

The lysophospholipid receptor group are members of the G protein-coupled receptor family of integral membrane proteins that are important for lipid signaling. In humans, there are eight LPL receptors, each encoded by a separate gene...

 receptors.

Examples of GIRKs include a subset of potassium channels in the heart, which, when activated by parasympathetic signals such as acetylcholine

Acetylcholine

The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 through M2 muscarinic receptors, causes an inward current of potassium, which slows down the heart rate

Heart rate

Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....

. These are called muscarinic potassium channels (I_KACh) and are heterotetramers composed of two GIRK1

KCNJ3

Potassium inwardly-rectifying channel, subfamily J, member 3, also known as KCNJ3 or Kir3.1, is a human gene.-See also:* G protein-coupled inwardly-rectifying potassium channel* Inward-rectifier potassium ion channel- External links :...

 and two GIRK4

KCNJ5

G protein-activated inward rectifier potassium channel 4 is a protein that in humans is encoded by the KCNJ5 gene and is a type of G protein-gated ion channel.-See also:* G protein-coupled inwardly-rectifying potassium channel...

subunits.