Effect of fatty acids on the membrane fluidity of cultured chick dorsal root ganglion measured by fluorescence photobleaching recovery

Takenaka, Toshifumi; Horie, Hidenori; Kawasaki, Yuki

doi:10.1002/neu.480140605

Cited by 17 publications

(7 citation statements)

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“…Takenaka et al (1987) saw no difference between saturated and unsaturated fatty acids in the attenuation of Na+ current, and attributed their effect to a disruption of the Na+ channel m gate produced by fluidization of the membrane. This attribution is supported by measurements which show increases in membrane fluidity as measured by fluorescence photobleaching recovery (Takenaka et al 1983), as well as cell membrane expansion (Horie, Kawasaki & Takenaka, 1987), following application of millimolar quantities of 2-decenoate (CII: 1), a compound shown to reduce Na+ current. When comparing the present results with those of Takenaka et al (1987) it is clear that they differ significantly in terms of effect (attenuation of Na+ current with a shift in activation kinetics) and in the means of their production (millimolar quantities of lipid).…”

mentioning

confidence: 86%

“…First, cis-fatty acids have been demonstrated to activate PKC in the absence of Ca2+ and phospholipid (Murakami & Routtenberg, 1985;Murakami et al 1986). Secondly, cis-fatty acids in monomeric form have been demonstrated to fluidize cellular membranes (Ahkong, Fisher, Tampion & Lucy, 1973;Takenaka, Horie & Kawasaki, 1983;Kitagawa, Endo & Kametani, 1985). Thirdly, cis-fatty acids, like all fatty acids, have the capacity to form micelles, which by fusing with the cellular membrane may disrupt membrane and ion channel function.…”

Section: Solutionsmentioning

confidence: 99%

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cis‐Fatty acids, which activate protein kinase C, attenuate Na+ and Ca2+ currents in mouse neuroblastoma cells.

Linden

Routtenberg

1989

The Journal of Physiology

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SUMMARY1. Activation of protein kinase C (PKC) by phorbol esters or diacylglycerols has been shown to modulate a number of ionic currents carried by Ca2±, K+ and Cl-.Recently, it has been demonstrated that PKC may be activated by cis-fatty acids in the absence of either phospholipid or Ca2 . We wished to determine if this new class of PKC-activating compound would also modulate ionic currents. To this end we applied the whole-cell voltage-clamp technique to NIE-1 15 neuroblastoma cells.2. Analysis of families of currents evoked under voltage clamp by depolarizing steps from a holding potential of -85 mV during external application of 5 1am-oleate (a cis-fatty acid) showed a 36% reduction of the peak inward current with no shift in either the peak or the reversal potential of the current-voltage relation and no alteration of outward current.3. External application of the cis-fatty acids oleate, linoleate and linolenate reversibly attenuated voltage-dependent Na+ current with approximate halfmaximal dose values of 2, 3, and 10/M respectively. Oleate was approximately 2 times more potent when applied internally (ED50 = 1 ,aM). Externally applied elaidate (a trans-isomer of oleate) and stearate (a saturated fatty acid) which do not activate PKC, had no effect. Since cis-fatty acids are known to fluidize membranes, as well as to activate PKC, we sought to dissociate these functions by applying compounds that fluidize membranes but do not activate PKC: methyloleate and lysophosphatidylcholine. Neither compound affected Na+ current when applied externally at concentrations of 1-50 /tM.4. In contrast to cis-fatty acids, three classical PKC activators, phorbol-12,13-dibutyrate (PDB), phorbol-12, 13-diacetate (PDA), and 1 ,2-oleoylacetylglycerol (OAG) were found to have no effect on the voltage-dependent Na+ current when applied externally at 10 nM-l ,UM (phorbol esters) or 1-150 /tM (OAG) for incubation periods up to 1 h.5. External application of the PKC inhibitors polymyxin B, H-7, sphingosine and staurosporine blocked the attenuation of the Na+ current by cis-fatty acid in a dosedependent manner, with maximal inhibition occurring at doses of 50, 10, 200 and 041 1M, respectively. The cyclic nucleotide-dependent protein kinase inhibitor H-8 * To whom correspondence should be addressed..AlS 7369 D. J. LINDEN AND A. ROUT"TENBERG was much less effective in blocking the cis-fatty acid effect. Polymyxin B and staurosporine were more potent when applied internally.6. Chronic (24 h) exposure to 1 ,UM phorbol-12-myristate-13-acetate (TPA) was employed to down-regulate PKC. This treatment did not alter the baseline characteristics of the isolated Na+ current, but was effective in blocking the attenuation of Na+ current produced by subsequent external application of ci8-fatty acid.7. To determine whether the distinction between cis-fatty acids and classical PKC activators was specific to the Na+ current, these compounds were applied externally to isolated Ca2+ currents. Both classes of compound attenuated both transient and susta...

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mentioning

confidence: 86%

Section: Solutionsmentioning

confidence: 99%

cis‐Fatty acids, which activate protein kinase C, attenuate Na+ and Ca2+ currents in mouse neuroblastoma cells.

Linden

Routtenberg

1989

The Journal of Physiology

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“…Some change in the steadystate properties of the membrane must be considered and obvious candidates are the surface free energy or surface tension, and the dipole potential at the surface. We have found that fatty acids increase membrane fluidity (Takenaka, Horie & Kawasaki, 1983). The lipid lateral motion of the membrane complex was increased about 40% by the application of 2-decenoic acid, whereas valeric acid caused much smaller changes in the lateral motion of the membrane lipids.…”

Section: Hodgkin-huxley Parameters and Membrane Fluiditymentioning

confidence: 98%

Effects of fatty acids on membrane currents in the squid giant axon

1987

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The effects of fatty acids on the ionic currents of the voltage-clamped squid giant axon were investigated using intracellular and extracellular application of the test substances. Fatty acids mainly suppress the Na current but have little effect on the K current. These effects are completely reversed after washing with control solution. The concentrations required to suppress the peak inward current by 50% and Hill number were determined for each fatty acid. ED50 decreased about 1/3 for each increase of one carbon atom. The standard free energy was -3.05 kJ mole-1 for CH2. The Hill number was 1.58 for 2-decenoic acid. The suppression effect of the fatty acids depends on the number of carbon atoms in the compounds and their chemical structure. Suppression of the Na current was clearly observed when the number of carbon atoms exceeded eight. When fatty acids of the same chain length were compared, 2-decenoic acid had strong inhibitory activity, but sebacic acid had no effect at all on the Na channel. The currents were fitted to equations similar to those proposed by Hodgkin and Huxley (J. Physiol. (London) 117:500-544, 1952) and the changes in the parameters of these equations in the presence of fatty acids were calculated. The curve of the steady-state activation parameter (m infinity) for the Na current against membrane potential and the time constant of activation (tau m) were shifted 20 mV in a depolarizing direction by the application of fatty acids. The time constant for inactivation (tau h) was almost no change by application of the fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…The physiological meaning of this shift is not yet clear but some change in the steady-state properties of the membrane must be considered and obvious candidates are the surface-free energy or surface tension and the dipole potential at the surface. The lipid lateral motion of the membrane complex was increased enormously by the application of mediumchain fatty acids (Takenaka, Horie & Kawasaki, 1983;Takenaka, et al, 1986). The suppression mechanism of the long-chain fatty acids might be the same as that of the medium-chain fatty acids (Takenaka et al, 1987).…”

Section: Hodgkin-huxley Parameter Of Long-chain Fatty Acidsmentioning

confidence: 99%

Effects of arachidonic acid and the other long-chain fatty acids on the membrane currents in the squid giant axon

et al. 1988

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The effects of arachidonic acid and some other long-chain fatty acids on the ionic currents of the voltage-clamped squid giant axon were investigated using intracellular application of the test substances. The effects of these acids, which are usually insoluble in solution, were examined by using alpha-cyclodextrin as a solvent, alpha-cyclodextrin itself had no effect on the excitable membrane. Arachidonic acid mainly suppresses the Na current but has little effect on the K current. These effects are completely reversed after washing with control solution. The concentration required to suppress the peak inward current by 50% (ED50) was 0.18 mM, which was 10 times larger than that of medium-chain fatty acids like 2-decenoic acid. The Hill number was 1.5 for arachidonic acid, which is almost the same value as for medium-chain fatty acids. This means that the mechanisms of the inhibition are similar in both long- and medium-chain fatty acids. When the long-chain fatty acids were compared, the efficacy of suppression of Na current was about the same value for arachidonic acid, docosatetraenoic acid and docosahexaenoic acid. The suppression effects of linoleic acid and linolenic acid on Na currents were one-third of that of arachidonic acid. Oleic acid had a small suppression effect and stearic acid had almost no effect on the Na current. The currents were fitted to equations similar to those proposed by Hodgkin and Huxley (Hodgkin, A.L., Huxley, A.F. (1952) J. Physiol (London) 117:500-544) and the change in the parameters of these equations in the presence of fatty acids were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

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Effect of fatty acids on the membrane fluidity of cultured chick dorsal root ganglion measured by fluorescence photobleaching recovery

Cited by 17 publications

References 5 publications

cis‐Fatty acids, which activate protein kinase C, attenuate Na+ and Ca2+ currents in mouse neuroblastoma cells.

cis‐Fatty acids, which activate protein kinase C, attenuate Na+ and Ca2+ currents in mouse neuroblastoma cells.

Effects of fatty acids on membrane currents in the squid giant axon

Effects of arachidonic acid and the other long-chain fatty acids on the membrane currents in the squid giant axon

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