ATP-sensitive potassium channel
potassium inwardly-rectifying channel, subfamily J, member 8 | |||||||
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Identifiers | |||||||
Symbol | Chr. 12 p12.1 | ||||||
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potassium inwardly-rectifying channel, subfamily J, member 11 | |||||||
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Identifiers | |||||||
Symbol | Chr. 11 p15.1 | ||||||
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ATP-binding cassette, sub-family C (CFTR/MRP), member 8 | |||||||
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Identifiers | |||||||
Symbol | Chr. 11 p15.1 | ||||||
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ATP-binding cassette, sub-family C (CFTR/MRP), member 9 | |||||||
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Identifiers | |||||||
Symbol | Chr. 12 p12.1 | ||||||
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An ATP-sensitive potassium channel (or KATP channel) is a type of potassium channel that is gated by intracellular nucleotides, ATP and ADP. ATP-sensitive potassium channels are composed of Kir6.x-type subunits and sulfonylurea receptor (SUR) subunits, along with additional components.[1] KATP channels are widely distributed in plasma membranes;[2] however some may also be found on subcellular membranes. These latter classes of KATP channels can be classified as being either sarcolemmal ("sarcKATP"), mitochondrial ("mitoKATP"), or nuclear ("nucKATP").
Discovery and structure
KATP channels were first identified in
SarcKATP are composed of eight protein subunits (
MitoKATP were first identified in 1991 by single-channel recordings of the inner mitochondrial membrane.[9] The molecular structure of mitoKATP is less clearly understood than that of sarcKATP. Some reports indicate that cardiac mitoKATP consist of Kir6.1 and Kir6.2 subunits, but neither SUR1 nor SUR2.[10][11] More recently, it was discovered that certain multiprotein complexes containing succinate dehydrogenase can provide activity similar to that of KATP channels.[12]
The presence of nucKATP was confirmed by the discovery that isolated patches of nuclear membrane possess properties, both kinetic and pharmacological, similar to
Sensor of cell metabolism
Regulation of gene expression
Four
Changes in the
A mechanism has been proposed for the cell's KATP reaction to
One significant implication of the link between cellular oxidative stress and increased KATP production is that overall potassium transport function is directly proportional to the membrane concentration of these channels. In cases of diabetes, KATP channels cannot function properly, and a marked sensitivity to mild cardiac ischemia and hypoxia results from the cells' inability to adapt to adverse oxidative conditions.[18]
Metabolite regulation
The degree to which particular compounds are able to regulate KATP channel opening varies with tissue type, and more specifically, with a tissue's primary metabolic substrate.
In
Mitochondrial KATP and the regulation of aerobic metabolism
Upon the onset of a cellular energy crisis, mitochondrial function tends to decline. This is due to alternating inner
Nuclear and sarcolemmal KATP channels also contribute to the endurance of and recovery from metabolic stress. In order to conserve energy, sarcKATP open, reducing the duration of the action potential while nucKATP-mediated Ca2+ concentration changes within the nucleus favor the expression of protective protein genes.[8]
Cardiovascular KATP channels and protection from ischemic injury
Cardiac ischemia, while not always immediately lethal, often leads to delayed cardiomyocyte death by necrosis, causing permanent injury to the heart muscle. One method, first described by Keith Reimer in 1986, involves subjecting the affected tissue to brief, non-lethal periods of ischemia (3–5 minutes) before the major ischemic insult. This procedure is known as ischemic preconditioning ("IPC"), and derives its effectiveness, at least in part, from KATP channel stimulation.
Both sarcKATP and mitoKATP are required for IPC to have its maximal effects. Selective mitoKATP blockade with 5-hydroxydecanoic acid ("5-HD") or MCC-134
Absence of sarcKATP, in addition to attenuating the benefits of IPC, significantly impairs the myocyte's ability to properly distribute Ca2+, decreasing sensitivity to
Upon further exploration of sarcKATP's role in
See also
References
- PMID 16865362.
- PMID 9558481.
- S2CID 31679373.
- S2CID 4340710.
- PMID 24906950.
- S2CID 26409797.
- PMID 12565699.
- ^ PMID 15694835.
- S2CID 4358756.
- PMID 14596790.
- PMID 9225262.
- PMID 15284438.
- PMID 12089327.
- S2CID 11851627.
- PMID 11145575.
- PMID 11420303.
- PMID 12791696.
- PMID 14737020.
- ^ PMID 18591420.
- PMID 10969823.
- S2CID 16641599.
- PMID 11717159.
- S2CID 19081999.
- S2CID 7442045.
- S2CID 56186961.
- S2CID 25717677.
- PMID 12271142.
- PMID 12122112.
- PMID 15034580.
Further reading
- Girard CA, Shimomura K, Proks P, Absalom N, Castano L, Perez De Nanclares G, Ashcroft FM (2006). "Functional analysis of six Kir6.2 (KCNJ11) mutations causing neonatal diabetes". Pflügers Arch. 453 (3): 323–32. PMID 17021801.
External links
- KCNJ11+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)