The Mitochondrial Potassium Cycle

Garlid, Keith D.; Pauček, Petr

doi:10.1080/15216540152845948

Cited by 49 publications

(28 citation statements)

References 54 publications

(58 reference statements)

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“…Enhanced K ϩ uptake through mitochondrial K ATP channels would lead to a lower ⌬⌿. This effect could promote a decline in mitochondrial ROS production (48,49). There is as yet no direct data on the role of mitochondrial K ATP channels in pancreatic ␤-cells; however, one would expect that the openers of mitochondrial K ATP will act similarly to UCP2 activation.…”

Section: Gdis and Adenine Nucleotides Regulation)mentioning

confidence: 99%

Does the Glucose-Dependent Insulin Secretion Mechanism Itself Cause Oxidative Stress in Pancreatic β-Cells?

2004

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Glucose-dependent insulin secretion (GDIS), reactive oxygen species (ROS) production, and oxidative stress in pancreatic ␤-cells may be tightly linked processes. Here we suggest that the same pathways used in the activation of GDIS (increased glycolytic flux, ATP-to-ADP ratio, and intracellular Ca 2؉ concentration) can dramatically enhance ROS production and manifestations of oxidative stress and, possibly, apoptosis. The increase in ROS production and oxidative stress produced by GDIS activation itself suggests a dual role for metabolic insulin secretagogues, as an initial sharp increase in insulin secretion rate can be accompanied by progressive ␤-cell injury. We propose that therapeutic strategies targeting enhancement of GDIS should be carefully considered in light of possible loss of ␤-cell function and mass.

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Section: Gdis and Adenine Nucleotides Regulation)mentioning

confidence: 99%

Does the Glucose-Dependent Insulin Secretion Mechanism Itself Cause Oxidative Stress in Pancreatic β-Cells?

2004

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“…: 503-725-8969; Fax: 503-725-3888; E-mail: garlid@pdx.edu. 1 The abbreviations used are: ⌬⌿, membrane potential; mitoK ATP , mitochondrial K ATP channel; mitoKIR, inward-rectifying channel subunit of mitoK ATP ; mitoSUR, sulfonylurea receptor subunit of mitoK ATP ; cellK ATP , ATP-dependent K ϩ channel; DEB, p-diethylaminoethylbenzoate; TPP, tetraphenylphosphonium; PBFI, potassium-binding benzofuran isophthalate; 5-HD, 5-hydroxydecanoic acid; holo-mitoKATP, mitoK ATP containing both of its subunits; N H , Hill coefficient.…”

Section: Methodsmentioning

confidence: 99%

Functional Distinctions between the Mitochondrial ATP-dependent K+ Channel (mitoKATP) and Its Inward Rectifier Subunit (mitoKIR)

Mironova

Negoda

Marinov

et al. 2004

Journal of Biological Chemistry

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101

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The ATP-sensitive potassium channel from the inner mitochondrial membrane (mitoK ATP ) is a highly selective conductor of K ؉ ions. When isolated in the presence of nonionic detergent and reconstituted in liposomes, mitoK ATP is inhibited with high affinity by ATP (K 1/2 ‫؍‬ 20 -30 M). We have suggested that holo-mitoK ATP is a heteromultimer consisting of an inwardly rectifying K The importance of the mitochondrial K ϩ cycle for volume regulation, reviewed by Garlid and Paucek (1) was recognized by Mitchell (2) long before any of the components of this cycle were discovered. K ϩ is driven into the matrix by the high membrane potential (⌬⌿) 1 generated by the proton-pumping electron transport system, and excess K ϩ is removed by the regulated K ϩ /H ϩ antiporter. Electrophoretic K ϩ influx occurs by diffusion and by means of ATP-sensitive potassium channel from the inner mitochondrial membrane (mitoK ATP ). At the high values of ⌬⌿ maintained by mitochondria, both of these processes increase exponentially with ⌬⌿ (3, 4) and are consequently very sensitive to fluctuations in ⌬⌿. These fluctuations, in turn, are high in tissues such as heart, which undergo large variations in energy demand and ATP synthesis rates (5). Thus, regulation of K ϩ influx and efflux pathways can be seen as a means of regulating volume in the face of the changing energy requirements of the cell. MitoK ATP plays more than a housekeeping role in cell physiology. There is now general agreement that mitoK ATP plays a key role in cardioprotection against ischemia-reperfusion injury (6, 7). The proposed mechanisms of this protective effect of mitoK ATP opening (5, 8, 9) are plausible; however, it is evident that more needs to be known about the functional properties of mitoK ATP before its role in vivo can be ascertained.By using a novel ethanol extraction technique, Mironova et al. (10) were the first to report reconstitution in lipid bilayer membranes of a 55-kDa K ϩ channel from mitochondria. Paucek et al. (3) used a detergent extraction technique and were the first to report reconstitution of mitoK ATP in liposomes. The latter channel was associated with two proteins of molecular mass 55 and 63 kDa, and we hypothesized that mitoK ATP is a heteromultimeric complex consisting of a 55-kDa inwardly rectifying K ϩ channel (mitoKIR) and a 63-kDa sulfonylurea receptor (mitoSUR), analogous to the plasma membrane ATPdependent K ϩ channel (cellK ATP ) (11,12). In this report, we focus on three interactions that address the key question of whether the 55-kDa K ϩ channel protein observed in the ethanol purification is the same as the 55-kDa protein purified with detergents. First, we show that UDP reverses ATP-inhibition of K ϩ flux mediated by both mitoKIR and mitoK ATP reconstituted in liposomes. Moreover, UDP exerts the same action in isolated mitochondria, and the affinities for the opening effect of UDP are about the same in each preparation. Second, we show that the mitoKIR opener p-diethylaminoethylbenzoate (DEB) also activates K ϩ flux via ...

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“…The cation flux is tightly regulated to avoid rupture of the mitochondrial membranes. This is accomplished by movement of K + out of the matrix through the K + /H + exchanger [19,20]. However, K + influx by mitoK ATP can transiently exceed the counterbalancing activity of the K + /H + exchanger, resulting in mitochondrial matrix swelling [21].…”

Section: 12mentioning

confidence: 99%

Mitochondrial K channels in cell survival and death

Ardehali¹,

O’Rourke²

2005

Journal of Molecular and Cellular Cardiology

196

151

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Since the discovery of the mitochondrial ATP-sensitive potassium channel (mitoK ATP ) more than 13 years ago, it has been implicated in the processes of ischemic preconditioning (IPC), apoptosis and mitochondrial matrix swelling. Different approaches have been employed to characterize the pharmacological profile of the channel, and these studies strongly suggest that cellular protection well correlates with the opening of mitoK ATP . However, there are many questions regarding mitoK ATP that remain to be answered. These include the very existence of mitoK ATP itself, its degree of importance in the process of IPC, its response to different pharmacological agents, and how its activation leads to the process of IPC and protection against cell death. Recent findings suggest that mitoK ATP may be a complex of multiple mitochondrial proteins, including some which have been suggested to be components of the mitochondrial permeability transition pore. However, the identity of the pore-forming unit of the channel and the details of the interactions between these proteins remain unclear. In this review, we attempt to highlight the recent advances in the physiological role of mitoK ATP and discuss the controversies and unanswered questions.

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The Mitochondrial Potassium Cycle

Cited by 49 publications

References 54 publications

Does the Glucose-Dependent Insulin Secretion Mechanism Itself Cause Oxidative Stress in Pancreatic β-Cells?

Does the Glucose-Dependent Insulin Secretion Mechanism Itself Cause Oxidative Stress in Pancreatic β-Cells?

Functional Distinctions between the Mitochondrial ATP-dependent K+ Channel (mitoKATP) and Its Inward Rectifier Subunit (mitoKIR)

Mitochondrial K channels in cell survival and death

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