Influence of histamine on the process of human trophoblast differentiation.
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Cell Differentiation↗
Biomedical subjects
A Szewczyk
Publications and source records attributed to A Szewczyk.
Quinine inhibits mitochondrial ATP-regulated potassium channel from bovine heart.
The mitochondrial ATP-regulated potassium (mitoK(ATP) channel has been suggested as trigger and effector in myocardial ischemic preconditioning. However, molecular and pharmacological properties of the mitoK(ATP) channel remain unclear. In the present study, single-channel activity was measured after reconstitution of the inner mitochondrial membrane from bovine ventricular myocardium into bilayer lipid membrane. After incorporation, a potassium-selective current was recorded with mean conductance of 103 +/- 9 pS in symmetrical 150 mM KCl. Single-channel activity of this reconstituted protein showed properties of the mitoK(ATP) channel: it was blocked by 500 microM ATP/Mg, activated by the potassium-channel opener diazoxide at 30 microM, inhibited by 50 microM glibenclamide or 150 microM 5-hydroxydecanoic acid, and was not affected by the plasma membrane ATP-regulated potassium-channel blocker HMR1098 at 100 microM. We observed that the mitoK(ATP) channel was blocked by quinine in the micromolar concentration range. The inhibition by quinine was additionally verified with the use of 86Rb+ flux experiments and submitochondrial particles. Quinine inhibited binding of the sulfonylurea derivative [3H]glibenclamide to the inner mitochondrial membrane. We conclude that quinine inhibits the cardiac mitoK(ATP) channel by acting on the mitochondrial sulfonylurea receptor.
Animals↗
Cellular distribution of nonionic micelles.
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Animals↗
Protective effects of the potassium channel opener-diazoxide against injury in neonatal rat ventricular myocytes.
The mitochondrial ATP-regulated potassium channel is present in the inner membrane of heart mitochondria. Similarly to plasma membrane K(ATP), the mitochondrial channel is inhibited by antidiabetic sulfonylureas and activated by potassium channel openers, such as diazoxide. In the present work, the cytoprotective properties of diazoxide on the H9c2 cardiac myoblast cell line and neonatal rat ventricular cardiomyocytes were analysed. It was observed that 100 micromol/l diazoxide protected neonatal rat ventricular cardiomyocytes, but not H9c2 myoblasts, against injury induced by hydrogen peroxide or simulated ischemia. Moreover, diazoxide prevented hydrogen peroxide-induced mitochondrial potential depolarisation in neonatal rat ventricular cardiomyocytes. Diazoxide, at the same time, did not affect the expression level of the anti-apoptotic protein bcl-2 in these cells. The protective effects of diazoxide were suppressed by 5-hydroxydecanoic acid, a potassium channel blocker. These observations suggest that activation of the mitochondrial ATP-regulated potassium channel plays an important role in protection of neonatal cardiomyocytes against injury.
Animals↗
Potassium channel openers depolarize hippocampal mitochondria.
We investigated the effect of the potassium channel openers diazoxide and RP66471 on mitochondrial membrane potential and mitochondrial respiration in digitonin-treated rat hippocampal homogenates. Both diazoxide and RP66471 induced a dose-dependent decrease of mitochondrial membrane potential. Concomitant with the depolarization was an increase of mitochondrial respiration. Furthermore, the mitochondrial membrane depolarization induced by diazoxide and RP66471 was significantly larger in the presence of potassium ions than in the presence of sodium ions. The diazoxide-induced (but not RP66471-induced) mitochondrial membrane depolarization was partially inhibited by blockers of the ATP-regulated potassium channel, 5-hydroxydecanoic acid or the antidiabetic sulfonylurea glibenclamide. In addition, the potassium channel openers diazoxide and RP66471 increased mitochondrial matrix volume and induced a release of cytochrome c from hippocampal mitochondria. These results indicate the presence of a mitochondrial ATP-regulated potassium channel in rat hippocampus being a target for potassium channel openers.
Adenosine Triphosphate↗
Effect of antimicrobial apomyoglobin 56-131 peptide on liposomes and planar lipid bilayer membrane.
The horse apomyoglobin 56-131 peptide is a convenient object for studies on the recently discovered antimicrobial activities of haem-binding protein fragments called haemocidins. The purpose of this study was to determine the effect of this peptide on planar lipid bilayer membranes and on liposomes of different lipid compositions. Micromolar concentrations of the apomyoglobin 56-131 fragment disrupt phosphatidylserine/phosphatidylethanolamine planar lipid bilayers without discrete conductance changes. The observed detergent-like action is dependent on peptide concentration; the lower amount of peptide resulted in longer bilayer lifetime. The cholesterol has an inhibitory effect on peptide-induced liposome lysis as shown by calcein release from liposomes. Additionally, there was considerable lytic activity on liposomes formed from anionic lipids of the sort found in bacterial membranes. Circular dichroism (CD) experiments showed that the peptide had a disordered structure in aqueous solutions and folds gradually to form helices in both membrane-mimetic trifluoroethanol solutions as well as in liposome suspensions. The features of the apomyoglobin 56-131 fragment that are similar to the cationic antimicrobial peptides acting in a 'carpet-like' manner are discussed.
Antimicrobial Cationic Peptides↗
Acidic pH-induced folding of annexin VI is a prerequisite for its insertion into lipid bilayers and formation of ion channels by the protein molecules.
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Annexin A6↗
ATP-sensitive K+ transport in adrenal chromaffin granules.
In the present study the influx of 86Rb+, a K+ analogue, was studied in mitochondria, microsomes and chromaffin granules prepared from adrenal gland medulla. The most active electrogenic 86Rb+ transport was found in the membrane fraction identified as chromaffin granules by marker enzyme estimation. The transport was found to be sensitive to ATP, ATP gamma S, ADP and to the triazine dyes, but not to AMP and cAMP. The inhibition induced by ATP was observed in the absence of externally added Mg2+, suggesting that a free nucleotide, rather than the ATP-Mg complex, was required for inhibition. Furthermore, the 86Rb+ influx was found to be inhibited by Mg2+ alone, but not by Ca2+ and antidiabetic sulfonylureas. The 86Rb+ influx was not stimulated by potassium channel openers. In conclusion, our results indicate that an electrogenic, ATP-sensitive potassium transport system operates in the chromaffin granule membrane.
Adenosine Triphosphate↗
Intracellular potassium and chloride channels: an update.
Channels selective for potassium or chloride ions are present in all intracellular membranes such as mitochondrial membranes, sarcoplasmic/endoplasmic reticulum, nuclear membrane and chromaffin granule membranes. They probably play an important role in events such as acidification of intracellular compartments and regulation of organelle volume. Additionally, intracellular ion channels are targets for pharmacologically active compounds, e.g. mitochondrial potassium channels interact with potassium channel openers such as diazoxide. This review describes current observations concerning the properties and functional roles of intracellular potassium and chloride channels.
Animals↗
Lipid metabolism as a target for potassium channel effectors.
K(+) channel effectors are widely used in the treatment of various diseases, including diabetes mellitus type II, hypertension, and cardiac arrhythmia. In addition, a constantly growing body of literature reveals that some of these substances, despite their direct effect on K(+) channels, may influence cellular lipid metabolism. As a result, membrane lipid content and cellular concentrations of lipid messengers are changed. Due to the dependence of K(+) channel activity on membrane lipids, these observations seem to be of particular importance not only to characterize secondary effects of K(+) channel effectors but also to understand the long-term effects of these agents on K(+) channel activity.
Anti-Arrhythmia Agents↗
[Intracellular ion channels: properties, function and experimental methodology].
Ion channels selective for potassium or chloride ions are present in membranes of intracellular organelles such as mitochondria, sarcoplasmic (endoplasmic) reticulum, nucleus, synaptic vesicles, and chromaffin, and zymogen granules. They are probably important in cellular events such as compensation of electrical charges during intracellular transport of Ca2+ and H+ and regulation of organelle volume changes. This review describes the basic properties, and current hypotheses concerning the functional role, and some aspects of experimental methodology of intracellular ion channels studies.
Animals↗
Mitochondrial potassium and chloride channels.
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 delta pH 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.
Adenosine Triphosphate↗
Modification of the mitochondrial sulfonylurea receptor by thiol reagents.
The purpose of this study was to investigate the effects exerted by thiol-modifying reagents on themitochondrial sulfonylurea receptor. The thiol-oxidizing agents (timerosal and 5, 5'-dithio-bis(2-nitrobenzoic acid)) were found to produce a large inhibition (70% to 80%) of specific binding of [(3)H]glibenclamide to the beef heart mitochondrial membrane. Similar effects were observed with membrane permeable (N-ethylmaleimide) and non-permeable (mersalyl) thiol modifying agents. Glibenclamide binding was also decreased by oxidizing agents (hydrogen peroxide) but not by reducing agents (reduced gluthatione, dithiothreitol and the 2,3-dihydroxy-1,4-dithiolbutane). The results suggest that intact thiol groups, facing the mitochondrial matrix, are essential for glibenclamide binding to the mitochondrial sulfonylurea receptor.
ATP-Binding Cassette Transporters↗
Mitochondrial ATP-dependent potassium channels. Viable candidate effectors of ischemic preconditioning.
Pharmacological evidence has implicated ATP-dependent potassium (KATP) channels in the mechanism of ischemic preconditioning; however, the effects of sarcolemmal KATP channels on excitability cannot account for the protection. KATP channels also exist in mitochondrial inner membrane. To test whether such channels play a role in cardioprotection, we simultaneously measured flavoprotein fluorescence, an index of mitochondrial redox state, and sarcolemmal KATP currents in intact rabbit ventricular myocytes. Our results show that diazoxide, a KATP channel opener, induced reversible oxidation of flavoproteins, but did not activate sarcolemmal KATP channels. This effect of diazoxide was blocked by 5-hydroxydecanoic acid (5-HD). We further verified that 5-HD is a selective blocker of the mitochondrial KATP channels. These methods have enabled us to demonstrate that the activity of mitochondrial KATP channels can be regulated by protein kinase C. In a cellular model of simulated ischemia, inclusion of diazoxide decreased the rate of cell death to about half of that in control. Such protection is inhibited by 5-HD. In conclusion, our results demonstrate that diazoxide targets mitochondrial but not sarcolemmal KATP channels, and imply that mitochondrial KATP channels may mediate preconditioning.
Animals↗
Mitochondria: a new target for K channel openers?
Potassium channel openers have diverse actions ranging from vasodilation to promotion of hair growth. These drugs can also render the heart, and most likely other tissues, resistant to ischaemic necrosis, raising the possibility that they might prove useful in myocardial infarction and stroke. New research points to mitochondrial ATP-dependent K+ channels, not their classical surface membrane counterparts, as the likely effectors of the cardioprotective effects of K+ channel openers. Here, the evidence implicating mitochondrial channels and the prospects for novel drug development are reviewed.
Adenosine Triphosphate↗
Adenosine 5'-triphosphate: an intracellular metabolic messenger.
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Adenosine Triphosphate↗
[Usefulness of determining urinary markers of early renal damage for monitoring nephrotoxicity during occupational exposure to mercury vapors].
Using nephelometry, concentration of albumin, IgG, transferrin, retinol binding protein (RBP) alpha 1-microglobulin were determined in urine of 83 males with history of occupational exposure to metallic mercury vapours from 0.6 to 37 years, and in 30 non-exposed males. The weighted average of mercury air concentrations was 0.028 mg/m3. Duration of occupational exposure to mercury vapours did not elevate urine excretion of proteins. The urine concentration of proteins in question were higher (especially beta 2-m) in workers with urine mercury concentration between 51 and 150 microliter-1 and highest in workers with urine mercury concentrations above 150 micrograms l-1 and the differences were significant. In addition, a positive correlations between urine mercury concentrations and alpha 1-m (r = 0.33) as well as between urine mercury concentration and albumin (r = 0.31) were observed. In conclusion, the determination of proteins in urine as markers of early renal damage may be useful for monitoring occupational exposure to mercury vapours, especially in the group of workers with elevated values of urine mercury concentrations.
Adult↗
Intracellular targets for antidiabetic sulfonylureas and potassium channel openers.
Antidiabetic sulfonylureas and potassium channel openers affect the activity of the ATP-regulated potassium channel (K(ATP) channel) present in the plasma membrane of various cells. This causes a broad spectrum of physiological responses, including the modulation of insulin release from pancreatic B-cells and the relaxation of smooth muscle. Recently, new targets for antidiabetic sulfonylureas and potassium channel openers were found in membranes of organelles, such as mitochondria and zymogen- and insulin-containing granules. By acting on these targets, the drugs modulate, independently of K(ATP) channel activity, insulin release from pancreatic B-cells, and they regulate K+ transport in mitochondria and zymogen granules. The interaction of sulfonylureas and potassium channel openers with intracellular targets gives additional basic information about their properties. Additionally, these studies could be important because of the medical applications of sulfonylureas and potassium channel openers.
Adenosine Triphosphate↗