Effect of Linoleic Acid Metabolites on Na+/K+ Pump Current in N20.1 Oligodendrocytes: Role of Membrane Fluidity

Ha, Joomi; Dobretsov, Maxim; Kurten, Richard C.; Grant, David F.; Stimers, Joseph R.

doi:10.1006/taap.2002.9435

Cited by 13 publications

(13 citation statements)

References 42 publications

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“…The result suggests that the proper functioning of the enzyme requires the presence of intracellular soluble molecules that were gradually washed out during the course of whole cell recordings. Rundown of sodium pump activity has also been described in ventricular myocytes (Gadsby and Nakao 1989;Ha et al 2002) and is insensitive to treatments of the protease inhibitors leupeptin or aprotinin (Gadsby and Nakao 1989).…”

Section: Modulation Of Sodium Pump Activitymentioning

confidence: 99%

Effects of Sodium Pump Activity on Spontaneous Firing in Neurons of the Rat Suprachiasmatic Nucleus

Wang¹,

Huang²

2006

Journal of Neurophysiology

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. Effects of sodium pump activity on spontaneous firing in neurons of the rat suprachiasmatic nucleus. J Neurophysiol 96: 109 -118, 2006. First published February 8, 2006 doi:10.1152/jn.01369.2005. Cell-attached and whole cell recording techniques were used to study the effects of electrogenic sodium pump on the excitability of rat suprachiasmatic nucleus (SCN) neurons. Blocking the sodium pump with the cardiac steroid strophanthidin or zero K ϩ increased the spontaneous firing of SCN neurons to different degrees with different recording modes, whereas turning the sodium pump into a nonselective cation channel with the marine toxin palytoxin invariably increased the spontaneous firing to the point of total blockade. Current-clamp recordings indicated that strophanthidin increased the rate of membrane depolarization and reduced the peak afterhyperpolarization potential (AHP), whereas zero K ϩ also increased the rate of depolarization, but enhanced the peak AHP. The dual effect of zero K ϩ was reflected by the biphasic time course of voltage responses to zero K ϩ : an inhibitory phase with enhanced peak AHP and slower firing, followed by a delayed excitatory phase with faster rate of membrane depolarization and faster firing. In the presence of strophanthidin to block the sodium pump, zero K ϩ consistently decreased firing by enhancing the peak AHP. Repetitive applications of K ϩ -free solution gradually turned the biphasic inhibitory-followed-by-excitatory voltage response into a monophasic inhibitory response in cells recorded with the whole cell (but not the cell-attached) mode, suggesting rundown of sodium pump activity. Taken together, the results suggest that spontaneous firing of SCN neurons is regulated by sodium pump activity as well as the AHP, and that sodium pump activity is modulated by intracellular soluble substances subject to rundown under the whole cell conditions.

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Section: Modulation Of Sodium Pump Activitymentioning

confidence: 99%

Effects of Sodium Pump Activity on Spontaneous Firing in Neurons of the Rat Suprachiasmatic Nucleus

Wang¹,

Huang²

2006

Journal of Neurophysiology

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“…Because all of these compounds are highly lipid soluble, it may be possible that these compounds exert their effects via interactions in the membrane that change membrane fluidity and indirectly alter I Na . In another study, both EOA and DHOA have also been shown to inhibit Na ϩ /K ϩ pump current in oligodendrocytes (Ha et al, 2002). This inhibition was also shown to have no correlation to membrane fluidity (Ha et al, 2002).…”

Section: Discussionmentioning

confidence: 98%

“…In another study, both EOA and DHOA have also been shown to inhibit Na ϩ /K ϩ pump current in oligodendrocytes (Ha et al, 2002). This inhibition was also shown to have no correlation to membrane fluidity (Ha et al, 2002).…”

Section: Discussionmentioning

confidence: 98%

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Differential Effects of Linoleic Acid Metabolites on Cardiac Sodium Current

Harrell

Stimers²

2002

J Pharmacol Exp Ther

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9,10-Epoxy-12-octadecenoic acid (EOA), a metabolite of linoleic acid, causes cardiac arrest in dogs. Other metabolites of linoleic acid also have toxic effects. This study investigates the mechanism of action of four of these compounds on cardiac Na ϩ current (I Na ). The whole-cell patch-clamp technique was used to investigate the effects of EOA, 9,10-dihydroxy-12-octadecenoic acid (DHOA), and their corresponding methyl esters (9,10-epoxy-12-octadecenoic methyl ester, EOM; and 9,10-dihydroxy-12-octadecenoic methyl ester, DHOM) on I Na in isolated adult rat ventricular myocytes. Extracellular application of each compound elicited a concentration-dependent inhibition of I Na . The dose-response curve yielded 50% inhibition concentrations of 301 Ϯ 117 M for DHOA, 41 Ϯ 6 M for DHOM, 34 Ϯ 5 M for EOA, and 160 Ϯ 41 M for EOM. Although there was no effect on activation, 50 M DHOM, EOA, and EOM significantly hyperpolarized the steady-state inactivation curve by approximately Ϫ6 mV. Furthermore, EOM significantly increased the slope of the steady-state inactivation curve. These compounds also seemed to stabilize the inactivated state because the time for recovery from inactivation was significantly slowed from a control value of 12.9 Ϯ 0.5 ms to 30.5 Ϯ 3.3, 31.4 Ϯ 1.4, and 20.5 Ϯ 1.0 ms by 50 M DHOM, EOA, and EOM, respectively. These compounds have multiple actions on Na ϩ channels and that despite their structural similarities their actions differ from each other. The steady-state block of I Na suggests that either the pore is being blocked or the channels are prevented from gating to the open state. In addition, these compounds stabilize the inactivated state and promote increased population of a slower inactivated state.The role of fatty acids in signaling processes is becoming increasingly important. Various fatty acids have been shown to alter several ion currents, including Na ϩ (Xiao et al., 1995;Kang and Leaf, 1996), Ca 2ϩ (Huang et al., 1992;Hashimoto et al., 1999) Bogdanov et al., 1998;Crumb et al., 1999), and Cl Ϫ (Ordway et al., 1991). Arachidonic acid (C20:4) has been widely studied for the actions of the parent compound as well as the extensive metabolic pathways, including the prostaglandins and leukotrienes. Although less widely studied, linoleic acid (C18:2) is a major component of cell membrane phospholipids and is subject to some of the same metabolic pathways. A linoleic acid metabolite (LAM) of interest is 9,10-epoxy-12-octadecenoic acid (EOA), also known as leukotoxin. EOA is formed by lipid autoxidation in the lungs (Sevanian et al., 1979) and by spontaneous reaction of oxygen radicals with linoleic acid in neutrophil membranes (Hayakawa et al., 1996) (Fig. 1). Although undetectable in normal patients (Hayakawa et al., 1990), EOA has been associated with acute respiratory distress syndrome in burn patients where it can reach plasma concentrations up to 300 M (mean peak plasma concentration of 99 Ϯ 25 M) (Kosaka et al., 1994). EOA has also been shown to cause cardiac arrest in dogs (Fukush...

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“…Although it was once thought that sEH acted to render the leukotoxins safe by converting them to their diols, it now appears that the diols (including 12,13-DHOME) are the morepotent cytotoxins ( 29 ). Thus, inhibition of sEH ameliorates many of the toxic effects of the leukotoxins ( 39 ), whereas 12,13-DHOME adversely affects the electrophysiology of cells including oligodendrocytes ( 40 ) and cardiac myocytes ( 41 ). In addition, both 12(13)-and 9(10)-EpOME can be metabolized to the THF-diols ( Fig.…”

Section: Lc/msmentioning

confidence: 99%

Metabolomics reveals increased isoleukotoxin diol (12,13-DHOME) in human plasma after acute Intralipid infusion

Edwards

Lawler

Nikolic³

et al. 2012

Journal of Lipid Research

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Effect of Linoleic Acid Metabolites on Na+/K+ Pump Current in N20.1 Oligodendrocytes: Role of Membrane Fluidity

Cited by 13 publications

References 42 publications

Effects of Sodium Pump Activity on Spontaneous Firing in Neurons of the Rat Suprachiasmatic Nucleus

Effects of Sodium Pump Activity on Spontaneous Firing in Neurons of the Rat Suprachiasmatic Nucleus

Differential Effects of Linoleic Acid Metabolites on Cardiac Sodium Current

Metabolomics reveals increased isoleukotoxin diol (12,13-DHOME) in human plasma after acute Intralipid infusion

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