The G protein-coupled inwardly-rectifying potassium channels (GIRKs) are a family of lipid-gated inward-rectifier potassium ion channels which are activated (opened) by the signaling lipid PIP2 and a

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

cascade starting with

ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...

-stimulated

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

s (GPCRs). GPCRs in turn release activated

G-protein G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their act ...

βγ- subunits ( G_βγ) from inactive

heterotrimeric G protein Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a Heteromer, heterotrimeric complex. The biggest no ...

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 membrane. G protein-coupled inwardly-rectifying potassium channels are a type of

G protein-gated ion channel G protein-gated ion channels are a family of transmembrane ion channels in neurons and atrial myocytes that are directly gated by G proteins. Overview of mechanisms and function Generally, G protein-gated ion channels are specific ion channe ...

s because of this direct interaction of G protein subunits with GIRK channels. The activation likely works by increasing the affinity of the channel for PIP2. In high concentration PIP2 activates the channel absent G-protein, but G-protein does not activate the channel absent PIP2. GIRK1 to GIRK3 are distributed broadly in the central nervous system, where their distributions overlap. GIRK4, instead, is found primarily in the heart.

Subtypes

Examples

A wide variety of G protein-coupled receptors activate GIRKs, including the M₂-muscarinic, A₁-adenosine, α₂-adrenergic, D₂-dopamine, μ- δ-, and κ-

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...

, 5-HT_1A serotonin,

somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-couple ...

galanin Galanin is a neuropeptide encoded by the ''GAL'' gene, that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three G protein-coupled receptors. Much of galanin's function ...

, m-Glu, GABA_B,

TAAR1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is an intracellular amine-activated and G protein-coupled receptor (GPCR) that is primarily ex ...

, CB₁ and CB₂, and

sphingosine-1-phosphate Sphingosine-1-phosphate (S1P) is a signaling sphingolipid, also known as lysosphingolipid. It is also referred to as a bioactive lipid mediator. Sphingolipids at large form a class of lipids characterized by a particular aliphatic aminoalcoho ...

receptors. Examples of GIRKs include a subset of potassium channels in the heart, which, when activated by

parasympathetic The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of t ...

signals such as

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...

through M2 muscarinic receptors, causes an outward current of potassium, which slows down the

heart rate Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and excr ...

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

GIRK4 G protein-activated inward rectifier potassium channel 4 (GIRK-4) is a protein that in humans is encoded by the ''KCNJ5'' gene and is a type of G protein-gated ion channel. Function Potassium channels are present in most mammalian cells, where ...

subunits.

References

External links

* {{ion channel modulators Ion channels