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1

Potassium channels in brain mitochondria

100%

Bednarczyk P.

|

issue 3

385-392

EN

Potassium channels are the most widely distributed class of ion channels. These channels are transmembrane proteins known to play important roles in both normal and pathophysiological functions in all cell types. Various potassium channels are recognised as potential therapeutic targets in the treatment of Parkinson's disease, Alzheimer's disease, brain/spinal cord ischaemia and sepsis. In addition to their importance as therapeutic targets, certain potassium channels are known for their beneficial roles in anaesthesia, cardioprotection and neuroprotection. Some types of potassium channels present in the plasma membrane of various cells have been found in the inner mitochondrial membrane as well. Potassium channels have been proposed to regulate mitochondrial membrane potential, respiration, matrix volume and Ca+ ion homeostasis. It has been proposed that mitochondrial potassium channels mediate ischaemic preconditioning in various tissues. However, the specificity of a pharmacological agents and the mechanisms underlying their effects on ischaemic preconditioning remain controversial. The following potassium channels from various tissues have been identified in the inner mitochondrial membrane: ATP-regulated (mitoKATP) channel, large conductance Ca2+-regulated (mitoBKCa) channel, intermediate conductance Ca2+-regulated (mitoIKCa) channel, voltage-gated (mitoKv1.3 type) channel, and twin-pore domain (mitoTASK-3) channel. It has been shown that increased potassium flux into brain mitochondria induced by either the mitoKATP channel or mitoBKCa channel affects the beneficial effects on neuronal cell survival under pathological conditions. Recently, differential distribution of mitoBKCa channels has been observed in neuronal mitochondria. These findings may suggest a neuroprotective role for the mitoBKCa channel in specific brain structures. This minireview summarises current data on brain mitochondrial potassium channels and the efforts to identify their molecular correlates.

2

Role of the mitochondrial ATP-sensitive K+ channels in cardioprotection.

88%

Ardehali H.

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vol. 51

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issue 2

379-390

EN

The mitochondrial ATP-sensitive K+ (mitoKATP) channel was discovered more than a decade ago. Since then, several pharmacological studies have identified agents that target this channel some of which selectively target mitoKATP. These and other studies have also suggested that mitoKATP plays a key role in the process of ischemic preconditioning (IPC) and prevention of apoptosis. The mechanism by which mitoKATP exerts its protective effects is unclear, however, changes in mitochondrial Ca2+ uptake and levels of reactive oxygen species, and mitochondrial matrix swelling are believed to be involved. Despite major advances, several important issues regarding mitoKATP remain unanswered. These questions include, but are not limited to: the molecular structure of mitoKATP, the downstream and upstream mechanisms that leads to IPC and cell death, and the pharmacological profile of the channel. This review attempts to provide an up-to-date overview of the role of mitoKATP in cardioprotection.

3

Mitochondrial potassium and chloride channels.

75%

Kicińska A., Dębska G., Kunz W., Szewczyk A.

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2000

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vol. 47

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issue 3

541-551

EN

Channels selective for potassium or chloride ions are present in inner mitochondrial membranes. They probably play an important role in mitochondrial events such as the formation of ΔpH and regulation of mitochondrial volume changes. Mitochondrial potassium and chloride channels could also be the targets for pharmacologically active compounds such as potassium channel openers and antidiabetic sulfonylureas. This review describes the properties, pharmacology, and current observations concerning the functional role of mitochondrial potassium and chloride channels.

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3 Acta Biochimica Polonica

1 2009

1 2004

1 2000

1 Ardehali H.

1 Bednarczyk P.

1 Dębska G.

1 Kicińska A.

1 Kunz W.

1 Szewczyk A.

Potassium channels in brain mitochondria

Role of the mitochondrial ATP-sensitive K+ channels in cardioprotection.

Mitochondrial potassium and chloride channels.