内向き整流性カリウムチャネル

関: inwardly rectifying potassium channel

WordNet

direct the flow of; "channel information towards a broad audience" (同)canalize, canalise
a television station and its programs; "a satellite TV channel"; "surfing through the channels"; "they offer more than one hundred channels" (同)television channel, TV channel
a passage for water (or other fluids) to flow through; "the fields were crossed with irrigation channels"; "gutters carried off the rainwater into a series of channels under the street"
(often plural) a means of communication or access; "it must go through official channels"; "lines of communication were set up between the two firms" (同)communication channel, line
a path over which electrical signals can pass; "a channel is typically what you rent from a telephone company" (同)transmission channel
a deep and relatively narrow body of water (as in a river or a harbor or a strait linking two larger bodies) that allows the best passage for vessels; "the ship went aground in the channel"
relating to or existing in the mind or thoughts; "a concern with inward reflections"
toward the center or interior; "move the needle further inwards!" (同)inwards
a light soft silver-white metallic element of the alkali metal group; oxidizes rapidly in air and reacts violently with water; is abundant in nature in combined forms occurring in sea water and in carnallite and kainite and sylvite (同)K, atomic number 19
electrical device that transforms alternating into direct current
a person who corrects or sets right; "a rectifier of prejudices"
official routes of communication; "you have to go through channels"

PrepTutorEJDIC

〈C〉『水路』(川・湾・運河の船の通行ができる深い部分) / 〈U〉河床・川底 / 〈C〉『海峡』 / 〈C〉みぞ(groove),(道路の)水渠(すいきょ) / 《複数形で》(運搬・伝達の)正式の経路(手続き);(一般に)経路 / 〈C〉(テレビ・ラジオの)チャンネル / …‘に'水路を開く / …‘に'みぞを堀る / …'を'伝える,流す
『内側へ』,『内部へ』 / 心の中へ,内省的に / 『内側』(『内部』)『の』(にある);内側(内部)への / 心の中の
ポタシウム,カリウム(金属元素;化学記号はK)
修正する人;調整器 / (電気)の整流器

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/29 22:43:26」(JST)

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[Wiki en表示]

Inwardly rectifying potassium channels (K_ir, IRK) are a specific subset of potassium selective ion channels. To date, seven subfamilies have been identified in various mammalian cell types.^[1] They are the targets of multiple toxins, and malfunction of the channels has been implicated in several diseases.^[2]

Overview of inward rectification

Figure 1. Whole-cell current recordings of K_ir2 inwardly-rectifying potassium channels expressed in an HEK293 cell. (This is a strongly inwardly rectifying current. Downward deflections are inward currents, upward deflections outward currents, and the x-axis is time in seconds.) There are 13 responses superimposed in this image. The bottom-most trace is current elicited by a voltage step to negative 60mV, and the top-most to positive 60mV, relative to the resting potential, which is close to the K⁺ reversal potential in this experimental system. Other traces are in 10mV increments between the two.

A channel that is "inwardly-rectifying" is one that passes current (positive charge) more easily in the inward direction (into the cell). It is thought that this current may play an important role in regulating neuronal activity, by helping to establish the resting membrane potential of the cell.

By convention, inward current is displayed in voltage clamp as a downward deflection, while an outward current (positive charge moving out of the cell) is shown as an upward deflection. At membrane potentials negative to potassium's reversal potential, inwardly rectifying K⁺ channels support the flow of positively charged K⁺ ions into the cell, pushing the membrane potential back to the resting potential. This can be seen in figure 1: when the membrane potential is clamped negative to the channel's resting potential (e.g. -60 mV), inward current flows (i.e. positive charge flows into the cell). However, when the membrane potential is set positive to the channel's resting potential (e.g. +60 mV), these channels pass very little charge out of the cell. Simply put, this channel passes much more current in the inward direction than the outward one. Note that these channels are not perfect rectifiers, as they can pass some outward current in the voltage range up to about 30 mV above resting potential.

These channels differ from the potassium channels that are typically responsible for repolarizing a cell following an action potential, such as the delayed rectifier and A-type potassium channels. Those more "typical" potassium channels preferentially carry outward (rather than inward) potassium currents at depolarized membrane potentials, and may be thought of as "outwardly rectifying." When first discovered, inward rectification was named "anomalous rectification" to distinguish it from outward potassium currents.^[3]

Inward rectifiers also differ from tandem pore domain potassium channels, which are largely responsible for "leak" K⁺ currents.^[4] Some inward rectifiers, termed "weak inward rectifiers," carry measurable outward K⁺ currents at voltages positive to the K⁺ reversal potential (corresponding to, but larger than, the small currents above the 0 nA line in figure 1). They, along with the "leak" channels, establish the resting membrane potential of the cell. Other inwardly rectifying channels, termed "strong inward rectifiers," carry very little outward current at all, and are mainly active at voltages negative to the reversal potential, where they carry inward current (the much larger currents below the 0 nA line in figure 1).^[5]

Mechanism of inward rectification

The phenomenon of inward rectification of K_ir channels is the result of high-affinity block by endogenous polyamines, namely spermine, as well as magnesium ions, that plug the channel pore at positive potentials, resulting in a decrease in outward currents. This voltage-dependent block by polyamines causes currents to be conducted well only in the inward direction. While the principal idea of polyamine block is understood, the specific mechanisms are still controversial.

Role of K_ir channels

K_ir channels are found in multiple cell types, including macrophages, cardiac and kidney cells, leukocytes, neurons, and endothelial cells. By mediating a small depolarizing K⁺ current at negative membrane potentials, they help establish resting membrane potential, and in the case of the K_ir3 group, they help mediate inhibitory neurotransmitter responses, but their roles in cellular physiology vary across cell types:

Location	Function
cardiac myocytes	K_ir channels close upon depolarization, slowing membrane repolarization and helping maintain a more prolonged cardiac action potential. This type of inward-rectifier channel is distinct from delayed rectifier K⁺ channels, which help repolarize nerve and muscle cells after action potentials; and potassium leak channels, which provide much of the basis for the resting membrane potential.
endothelial cells	K_ir channels are involved in regulation of nitric oxide synthase.
kidneys	K_ir export surplus potassium into collecting tubules for removal in the urine, or alternatively may be involved in the reuptake of potassium back into the body.
neurons and in heart cells	G-protein activated IRKs (K_ir3) are important regulators, modulated by neurotransmitters. A mutation in the GIRK2 channel leads to the weaver mouse mutation. "Weaver" mutant mice are ataxic and display a neuroinflammation-mediated degeneration of their dopaminergic neurons.^[6] Relative to non-ataxic controls, Weaver mutants have deficits in motor coordination and changes in regional brain metabolism.^[7] Weaver mice have been examined in labs interested in neural development and disease for over 30 years.
pancreatic beta cells	K_ATP channels (composed of K_ir6.2 and SUR1 subunits) control insulin release.

Biochemistry of K_ir channels

There are seven subfamilies of K_ir channels, denoted as K_ir1 - K_ir7.^[1] Each subfamily has multiple members (i.e. K_ir2.1, K_ir2.2, K_ir2.3, etc.) that have nearly identical amino acid sequences across known mammalian species.

K_ir channels are formed from as homotetrameric membrane proteins. Each of the four identical protein subunits is composed of two membrane-spanning alpha helices (M1 and M2). Heterotetramers can form between members of the same subfamily (i.e. K_ir2.1 and K_ir2.3) when the channels are overexpressed.

Diversity

Gene	Protein	Aliases	Associated subunits
KCNJ1	K_ir1.1	ROMK1	NHERF2
KCNJ2	K_ir2.1	IRK1	K_ir2.2, K_ir4.1, PSD-95, SAP97, AKAP79
KCNJ12	K_ir2.2	IRK2	K_ir2.1 and K_ir2.3 to form heteromeric channel, auxiliary subunit: SAP97, Veli-1, Veli-3, PSD-95
KCNJ4	K_ir2.3	IRK3	K_ir2.1 and K_ir2.3 to form heteromeric channel, PSD-95, Chapsyn-110/PSD-93
KCNJ14	K_ir2.4	IRK4	K_ir2.1 to form heteromeric channel
KCNJ3	K_ir3.1	GIRK1, KGA	K_ir3.2, K_ir3.4, K_ir3.5, K_ir3.1 is not functional by itself
KCNJ6	K_ir3.2	GIRK2	K_ir3.1, K_ir3.3, K_ir3.4 to form heteromeric channel
KCNJ9	K_ir3.3	GIRK3	K_ir3.1, K_ir3.2 to form heteromeric channel
KCNJ5	K_ir3.4	GIRK4	K_ir3.1, K_ir3.2, K_ir3.3
KCNJ10	K_ir4.1	K_ir1.2	K_ir4.2, K_ir5.1, and K_ir2.1 to form heteromeric channels
KCNJ15	K_ir4.2	K_ir1.3
KCNJ16	K_ir5.1	BIR 9
KCNJ8	K_ir6.1	K_ATP	SUR2B
KCNJ11	K_ir6.2	K_ATP	SUR1, SUR2A, and SUR2B
KCNJ13	K_ir7.1	K_ir1.4

Diseases related to K_ir channels

Persistent hyperinsulinemic hypoglycemia of infancy is related to autosomal recessive mutations in K_ir6.2. 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 K_ir 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 K_ir2.1. Depending on the mutation, it can be dominant or recessive. It is characterized by periodic paralysis, cardiac arrhythmias and dysmorphic features. (See also KCNJ2)
Barium poisoning is likely due to its ability to block K_ir channels.
Atherosclerosis (heart disease) may be related to K_ir channels. The loss of K_ir currents in endothelial cells is one of the first known indicators of atherogenesis (the beginning of heart disease).
Thyrotoxic hypokalaemic periodic paralysis has been linked to altered K_ir2.6 function.^[8]

References

^ ^a ^b Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA (2005). "International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacol Rev 57 (4): 509–26. doi:10.1124/pr.57.4.11. PMID 16382105.
^ Abraham MR, Jahangir A, Alekseev AE, Terzic A (November 1, 1999). "Channelopathies of inwardly rectifying potassium channels". FASEB J 13 (14): 1901–10. PMID 10544173. http://www.fasebj.org/cgi/content/full/13/14/1901.
^ Bertil Hille (2001). Ion Channels of Excitable Membranes 3rd ed. (Sinauer: Sunderland, MA), p. 151. ISBN 0-87893-321-2.
^ Hille, p. 155.
^ Hille, p. 153.
^ Peng J, Xie L, Stevenson FF et al. (2006). "Nigrostriatal dopaminergic neurodegeneration in the weaver mouse is mediated via neuroinflammation and alleviated by minocycline administration". J. Neurosci. 26 (45): 11644–51. doi:10.1523/JNEUROSCI.3447-06.2006. PMID 17093086.
^ Strazielle C, Deiss V, Naudon L, Raisman-Vozari R, Lalonde R. (2006). "Regional brain variations of cytochrome oxidase activity and motor coordination in Girk2(Wv) (Weaver) mutant mice.". Neuroscience 142 (2): 437–49. doi:10.1016/j.neuroscience.2006.06.011. PMID 16844307.
^ [1]

External links

Inward+Rectifier+Potassium+Channels at the US National Library of Medicine Medical Subject Headings (MeSH).
"Inwardly Recifying Potassium Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/IC/FamilyMenuForward?familyId=17.
UMich Orientation of Proteins in Membranes families/family-85 - Spatial positions of inward rectifier potassium channels in membranes.

UpToDate Contents

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English Journal

G protein-gated inwardly rectifying potassium (KIR 3) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites.

Nakamura A, Fujita M, Ono H, Hongo Y, Kanbara T, Ogawa K, Morioka Y, Nishiyori A, Shibasaki M, Mori T, Suzuki T, Sakaguchi G, Kato A, Hasegawa M.Author information Pain & Neurology, Medicinal Research Laboratories, Shionogi Co., Ltd., Osaka, Japan; Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.AbstractBACKGROUND AND PURPOSE: Oxycodone and morphine are μ-opioid receptor agonists prescribed to control moderate-to-severe pain. Previous studies suggested that these opioids exhibit different analgesic profiles. We hypothesized that distinct mechanisms mediate the differential effects of these two opioids and investigated the role of G protein-gated inwardly rectifying potassium (KIR 3 also known as GIRK) channels in their antinociceptive effects.
British journal of pharmacology.Br J Pharmacol.2014 Jan;171(1):253-64. doi: 10.1111/bph.12441.
BACKGROUND AND PURPOSE: Oxycodone and morphine are μ-opioid receptor agonists prescribed to control moderate-to-severe pain. Previous studies suggested that these opioids exhibit different analgesic profiles. We hypothesized that distinct mechanisms mediate the differential effects of these two opi
PMID 24117458

Peripheral G protein-coupled inwardly rectifying potassium channels are involved in δ-opioid receptor-mediated anti-hyperalgesia in rat masseter muscle.

Chung MK, Cho YS, Bae YC, Lee J, Zhang X, Ro JY.Author information Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, USA.AbstractBACKGROUND: Although the efficacy of peripherally administered opioid has been demonstrated in preclinical and clinical studies, the underlying mechanisms of its anti-hyperalgesic effects are poorly understood. G protein-coupled inwardly rectifying potassium (GIRK) channels are linked to opioid receptors in the brain. However, the role of peripheral GIRK channels in analgesia induced by peripherally administered opioid, especially in trigeminal system, is not clear.
European journal of pain (London, England).Eur J Pain.2014 Jan;18(1):29-38. doi: 10.1002/j.1532-2149.2013.00343.x. Epub 2013 Jun 6.
BACKGROUND: Although the efficacy of peripherally administered opioid has been demonstrated in preclinical and clinical studies, the underlying mechanisms of its anti-hyperalgesic effects are poorly understood. G protein-coupled inwardly rectifying potassium (GIRK) channels are linked to opioid rece
PMID 23740773

Somatic ATP1A1, ATP2B3, and KCNJ5 Mutations in Aldosterone-Producing Adenomas.

Williams TA, Monticone S, Schack VR, Stindl J, Burrello J, Buffolo F, Annaratone L, Castellano I, Beuschlein F, Reincke M, Lucatello B, Ronconi V, Fallo F, Bernini G, Maccario M, Giacchetti G, Veglio F, Warth R, Vilsen B, Mulatero P.Author information Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Torino, Torino, Italy. tracyann.williams@unito.it.AbstractAldosterone-producing adenomas (APAs) cause a sporadic form of primary aldosteronism and somatic mutations in the KCNJ5 gene, which encodes the G-protein-activated inward rectifier K(+) channel 4, GIRK4, account for ≈40% of APAs. Additional somatic APA mutations were identified recently in 2 other genes, ATP1A1 and ATP2B3, encoding Na(+)/K(+)-ATPase 1 and Ca(2+)-ATPase 3, respectively, at a combined prevalence of 6.8%. We have screened 112 APAs for mutations in known hotspots for genetic alterations associated with primary aldosteronism. Somatic mutations in ATP1A1, ATP2B3, and KCNJ5 were present in 6.3%, 0.9%, and 39.3% of APAs, respectively, and included 2 novel mutations (Na(+)/K(+)-ATPase p.Gly99Arg and GIRK4 p.Trp126Arg). CYP11B2 gene expression was higher in APAs harboring ATP1A1 and ATP2B3 mutations compared with those without these or KCNJ5 mutations. Overexpression of Na(+)/K(+)-ATPase p.Gly99Arg and GIRK4 p.Trp126Arg in HAC15 adrenal cells resulted in upregulation of CYP11B2 gene expression and its transcriptional regulator NR4A2. Structural modeling of the Na(+)/K(+)-ATPase showed that the Gly99Arg substitution most likely interferes with the gateway to the ion binding pocket. In vitro functional assays demonstrated that Gly99Arg displays severely impaired ATPase activity, a reduced apparent affinity for Na(+) activation of phosphorylation and K(+) inhibition of phosphorylation that indicate decreased Na(+) and K(+) binding, respectively. Moreover, whole cell patch-clamp studies established that overexpression of Na(+)/K(+)-ATPase Gly99Arg causes membrane voltage depolarization. In conclusion, somatic mutations are common in APAs that result in an increase in CYP11B2 gene expression and may account for the dysregulated aldosterone production in a subset of patients with sporadic primary aldosteronism.
Hypertension.Hypertension.2014 Jan;63(1):188-95. doi: 10.1161/HYPERTENSIONAHA.113.01733. Epub 2013 Sep 30.
Aldosterone-producing adenomas (APAs) cause a sporadic form of primary aldosteronism and somatic mutations in the KCNJ5 gene, which encodes the G-protein-activated inward rectifier K(+) channel 4, GIRK4, account for ≈40% of APAs. Additional somatic APA mutations were identified recently in 2 other
PMID 24082052

Japanese Journal

Genetic Background of Catecholaminergic Polymorphic Ventricular Tachycardia in Japan

Kawamura Mihoko,Ohno Seiko,Naiki Nobu,Nagaoka Iori,Dochi Kenichi,Wang Qi,Hasegawa Kanae,Kimura Hiromi,Miyamoto Akashi,Mizusawa Yuka,Itoh Hideki,Makiyama Takeru,Sumitomo Naokata,Ushinohama Hiroya,Oyama Kotaro,Murakoshi Nobuyuki,Aonuma Kazutaka,Horigome Hitoshi,Honda Takafumi,Yoshinaga Masao,Ito Makoto,Horie Minoru
Circulation Journal, 2013
… Methods and Results: In 50 Japanese probands from unrelated families who satisfied clinical criteria for CPVT, genetic testing was conducted in all exons on 3 CPVT-related genes: cardiac ryanodine receptor 2 (RYR2), calsequestrin 2 (CASQ2) and inward rectifier potassium channel 2 (KCNJ2), and the clinical features between RYR2-genotyped and -non-genotyped patient groups were compared. …
NAID 130003361749

Disruption of the Arabidopsis thaliana Inward-Rectifier K^+ Channel AKT1 Improves Plant Responses to Water Stress

Nieves-Cordones Manuel,Caballero Fernando,Martinez Vicente [他],RUBIO Francisco
Plant and cell physiology 53(2), 423-432, 2012-02-01
NAID 10030308854

Alternations of Transient Outward K+ Current (Ito) in Type 2 Diabetic Ventricular Cardiomyocytes

Sato Tatsuya,Kobayashi Takeshi,Miura Tetsuji,Tohse Noritsugu
Journal of Arrhythmia 27(Supplement), OP43_3-OP43_3, 2011
… Although cardiac ion channel remodeling has been reported in type 1 diabetes mellitus (T1DM), modification of the channels by type 2 DM (T2DM) is poorly understood. … Here we characterized ion channel properties in cardiomyocytes of OLETF, a rat model of obese T2DM. … current and inward rectifier K+ …
NAID 130002130172

Related Pictures

★リンクテーブル★

リンク元	「内向き整流性カリウムチャネル」「inwardly rectifying potassium channel」
関連記事	「channel」「rectifier」「inward」

「内向き整流性カリウムチャネル」

Inward rectifier potassium channel N-terminal
Identifiers
Symbol	IRK_N
Pfam	PF08466
InterPro	IPR013673
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

Inward rectifier potassium channel
	crystal structure of an inward rectifier potassium channel
Identifiers
Symbol	IRK
Pfam	PF01007
Pfam clan	CL0030
InterPro	IPR013521
SCOP	1n9p
SUPERFAMILY	1n9p
TCDB	1.A.2
OPM superfamily	8
OPM protein	3sya
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary