Inwardly rectifing potassium channels (Kir or IRK) are potassium selective ion channels. To date, seven subfamilies have been identified in various mammalian cell types. They are the targets of multiple toxins, and have been implicated in several diseases.

Function of Kir channels

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Kir channels are found in multiple cell types, including macrophages, cardiac and kidney cells, leukocytes, neurons and endothelial cells. Their roles in cellular physiology vary across cell types.

• In the heart, brain and skeletal muscle, Kir channels are believed to repolarize cells after action potentials. These channels also provide much of the basis of the resting membrane potential.

• In endothelial cells, Kir channels are involved in regulation of nitric oxide synthase.

• In the kidneys, Kir export surplus potassium into collecting tubules for removal in the urine, or alernatively may be involved in the reuptake of potassium back into the body.

Diseases related to Kir channels

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• Persistent hyperinsulinemic hypoglycemia of infancy is related to autosomal recessive mutations in Kir6.2. Certain mutations of this gene diminish the channel's ability to regulate insulin secretion, leading to hypoglycemia.

• Bartter's syndrome can be caused by mutations in Kir channels. This condition is characterized by the inability of kidneys to recycle potassium, causing low levels of potassium in the body.

• Andersen's syndrome is a rare condition caused by multiple mutations of Kir2.1. Depending on the mutation, it can be dominant or recessive. It is characterized by periodic paralysis, cardiac arrhythmias and dysmorphic features.

• Barium poisoning is likely due to its ability to block Kir channels.

• Atherosclerosis (heart disease) may be related to Kir channels. The loss of Kir currents in endothelial cells is one of the first known indicators of atherogenesis (the beginning of heart disease).

Definition of inward rectification

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These channels are termed inwardly rectifying - because they rectify current in the inward direction. This means that under equal but opposite electrochemical potentials, these channels will pass more inward current than they do outward current (The current is created by the flow of K+ ions down their electrochemical gradient) Under physiological conditions these channels allow outward potassium flow only when cells are near their resting potential, but these channels are blocked when the cells are depolarized. Hence these channels do not mediate the inward flow of potassium as was earlier suggested.

Biochemistry of Kir channels

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There are seven subfamilies of Kir channels, denoted as Kir1 - Kir7. Each subfamily has multiple members (i.e. Kir2.1, Kir2.2, Kir2.3, etc) that have nearly identical amino acid sequences across known mammalian species.

Kir channels are formed from as homotetrameric membrane proteins. Each of the four identical protein subunits is composed of two membrane spaning alpha helices (M1 and M2). Heterotetramers can form between members of the same subfamily (ie Kir2.1 and Kir2.3) when the channels are overexpressed, but it is unlikely that this occurs in vivo.

Ion channels | Biology

Sources

Abraham, R; A Jahangir; A Alekseev; A Terzic "Channelopathies of inwardly rectifying potassium channels" The FASEB Journal. 1999;13:1901-1910