Effects of saturated long-chain N-acylethanolamines on voltage-dependent Ca2+ fluxes in rabbit T-tubule membranes

Öz, Murat; Alptekin, Alp; Tchugunova, Yulia; Dinç, Meral

doi:10.1016/j.abb.2004.11.010

Cited by 16 publications

(8 citation statements)

References 32 publications

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“…However, they have been associated with the inhibition of neurodegenerative diseases 9 and in bone marrow cell regeneration 10. Docosanoyl ethanolamide, a saturated N-acylethanolamide (endocannabinoid) that modulates voltage-dependent Ca(2+) channels 11 was found to be uniquely up-regulated in differentiated cardiomyocytes.…”

Section: Resultsmentioning

confidence: 99%

Metabolic oxidation regulates embryonic stem cell differentiation

et al. 2010

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Metabolites offer an important unexplored complement to understanding the pluripotency of stem cells. Using mass spectrometry-based metabolomics, we show that embryonic stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. By monitoring the reduced and oxidized glutathione ratio as well as ascorbic acid levels, we demonstrate that the stem cell redox status is regulated during differentiation. Based on the oxidative biochemistry of the unsaturated metabolites, we experimentally manipulated specific pathways in embryonic stem cells while monitoring the effects on differentiation. Inhibition of the eicosanoid signaling pathway promoted pluripotency and maintained levels of unsaturated fatty acids. In contrast, downstream oxidized metabolites (e.g., neuroprotectin D1) and substrates of pro-oxidative reactions (e.g., acyl-carnitines), promoted neuronal and cardiac differentiation. We postulate that the highly unsaturated metabolome sustained by stem cells makes them particularly attuned to differentiate in response to in vivo oxidative processes such as inflammation.

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Section: Resultsmentioning

confidence: 99%

Metabolic oxidation regulates embryonic stem cell differentiation

et al. 2010

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“…We have previously reported that major NAE species, including AEA, produced during ischaemia have significant effects on the amplitudes and kinetics of APs and accompanying ionic currents that could account for the negative ionotropic actions of these compounds on ventricular myocytes (Voitychuk et al ., ). For example, functions of voltage‐gated Ca 2+ (Oz et al ., ); (Oz et al ., 2004; 2005; Alptekin et al ., ; Voitychuk et al ., ) and Na + (Gulaya et al ., ; Voitychuk et al ., ) channels are modulated by NAEs. In the concentration range used in our study, AEA inhibited the function of various cardiac ion channels in cannabinoid receptor‐independent manner.…”

Section: Discussionmentioning

confidence: 99%

Effects of the endogenous cannabinoid anandamide on voltage‐dependent sodium and calcium channels in rat ventricular myocytes

Kury

Voitychuk

Yang

et al. 2014

British J Pharmacology

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BACKGROUND AND PURPOSEThe endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) exerts negative inotropic and antiarrhythmic effects in ventricular myocytes. EXPERIMENTAL APPROACHWhole-cell patch-clamp technique and radioligand-binding methods were used to analyse the effects of anandamide in rat ventricular myocytes. KEY RESULTSIn the presence of 1-10 μM AEA, suppression of both Na + and L-type Ca 2+ channels was observed. Inhibition of Na + channels was voltage and Pertussis toxin (PTX) -independent. Radioligand-binding studies indicated that specific binding of [ 3 H] batrachotoxin (BTX) to ventricular muscle membranes was also inhibited significantly by 10 μM metAEA, a non-metabolized AEA analogue, with a marked decrease in Bmax values but no change in Kd. Further studies on L-type Ca 2+ channels indicated that AEA potently inhibited these channels (IC50 0.1 μM) in a voltage-and PTX-independent manner. AEA inhibited maximal amplitudes without affecting the kinetics of Ba 2+ currents. MetAEA also inhibited Na + and L-type Ca 2+ currents. Radioligand studies indicated that specific binding of [ CONCLUSION AND IMPLICATIONSResults indicate that AEA inhibited the function of voltage-dependent Na + and L-type Ca 2+ channels in rat ventricular myocytes, independent of CB1 and CB2 receptor activation.

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“…AA inhibits native L-current in a variety of systems: cardiac muscle (Petit-Jacques and Hartzell, 1996; Xiao et al, 1997; Liu, 2007), skeletal muscle T-tubule membranes (Oz et al, 2005), smooth muscle (Shimada and Somlyo, 1992), SCG (Liu and Rittenhouse, 2000; Liu et al, 2001), photoreceptors (Vellani et al, 2000), and retinal glial cells (Bringmann et al, 2001). No consensus of mechanism exists as to how AA inhibits L-channel activity, whether directly, through AA metabolites, or via AA activating a phosphatase.…”

Section: Discussionmentioning

confidence: 99%

Arachidonic acid inhibition of L-type calcium (CaV1.3b) channels varies with accessory CaVβ subunits

Roberts-Crowley

Rittenhouse

2009

Journal of General Physiology

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Arachidonic acid (AA) inhibits the activity of several different voltage-gated Ca2+ channels by an unknown mechanism at an unknown site. The Ca2+ channel pore-forming subunit (CaVα1) is a candidate for the site of AA inhibition because T-type Ca2+ channels, which do not require accessory subunits for expression, are inhibited by AA. Here, we report the unanticipated role of accessory CaVβ subunits on the inhibition of CaV1.3b L-type (L-) current by AA. Whole cell Ba2+ currents were measured from recombinant channels expressed in human embryonic kidney 293 cells at a test potential of −10 mV from a holding potential of −90 mV. A one-minute exposure to 10 µM AA inhibited currents with β1b, β3, or β4 58, 51, or 44%, respectively, but with β2a only 31%. At a more depolarized holding potential of −60 mV, currents were inhibited to a lesser degree. These data are best explained by a simple model where AA stabilizes CaV1.3b in a deep closed-channel conformation, resulting in current inhibition. Consistent with this hypothesis, inhibition by AA occurred in the absence of test pulses, indicating that channels do not need to open to become inhibited. AA had no effect on the voltage dependence of holding potential–dependent inactivation or on recovery from inactivation regardless of CaVβ subunit. Unexpectedly, kinetic analysis revealed evidence for two populations of L-channels that exhibit willing and reluctant gating previously described for CaV2 channels. AA preferentially inhibited reluctant gating channels, revealing the accelerated kinetics of willing channels. Additionally, we discovered that the palmitoyl groups of β2a interfere with inhibition by AA. Our novel findings that the CaVβ subunit alters kinetic changes and magnitude of inhibition by AA suggest that CaVβ expression may regulate how AA modulates Ca2+-dependent processes that rely on L-channels, such as gene expression, enzyme activation, secretion, and membrane excitability.

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Effects of saturated long-chain N-acylethanolamines on voltage-dependent Ca2+ fluxes in rabbit T-tubule membranes

Cited by 16 publications

References 32 publications

Metabolic oxidation regulates embryonic stem cell differentiation

Metabolic oxidation regulates embryonic stem cell differentiation

Effects of the endogenous cannabinoid anandamide on voltage‐dependent sodium and calcium channels in rat ventricular myocytes

Arachidonic acid inhibition of L-type calcium (CaV1.3b) channels varies with accessory CaVβ subunits

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