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

Lina T. Al Kury, Oleg I. Voitychuk, Keun Hang Susan Yang, Faisal T. Thayyullathil, Petro Doroshenko, Ali M. Ramez, Yaroslav M. Shuba, Sehamuddin Galadari, Frank Christopher Howarth, Murat Oz

    Research output: Contribution to journalArticle

    Abstract

    Background and Purpose The endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) exerts negative inotropic and antiarrhythmic effects in ventricular myocytes. Experimental Approach Whole-cell patch-clamp technique and radioligand-binding methods were used to analyse the effects of anandamide in rat ventricular myocytes. Key Results In the presence of 1-10 μM AEA, suppression of both Na+ and L-type Ca2+ channels was observed. Inhibition of Na+ channels was voltage and Pertussis toxin (PTX) - independent. Radioligand-binding studies indicated that specific binding of [3H] 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 Ca2+ 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 Ba2+ currents. MetAEA also inhibited Na+ and L-type Ca2+ currents. Radioligand studies indicated that specific binding of [3H]isradipine, was inhibited significantly by metAEA. (10 μM), changing Bmax but not Kd. Conclusion and Implications Results indicate that AEA inhibited the function of voltage-dependent Na+ and L-type Ca2+ channels in rat ventricular myocytes, independent of CB1 and CB2 receptor activation.

    Original languageEnglish (US)
    Pages (from-to)3485-3498
    Number of pages14
    JournalBritish Journal of Pharmacology
    Volume171
    Issue number14
    DOIs
    StatePublished - Jan 1 2014

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    Cannabinoids
    Sodium Channels
    Calcium Channels
    Muscle Cells
    Pertussis Toxin
    Batrachotoxins
    Isradipine
    Cannabinoid Receptor CB2
    Cannabinoid Receptor CB1
    Endocannabinoids
    Patch-Clamp Techniques
    Inhibitory Concentration 50
    Muscles
    Membranes
    anandamide

    Keywords

    • endocannabinoid
    • ventricular myocyte

    ASJC Scopus subject areas

    • Pharmacology

    Cite this

    Al Kury, L. T., Voitychuk, O. I., Yang, K. H. S., Thayyullathil, F. T., Doroshenko, P., Ramez, A. M., ... Oz, M. (2014). Effects of the endogenous cannabinoid anandamide on voltage-dependent sodium and calcium channels in rat ventricular myocytes. British Journal of Pharmacology, 171(14), 3485-3498. https://doi.org/10.1111/bph.12734

    Effects of the endogenous cannabinoid anandamide on voltage-dependent sodium and calcium channels in rat ventricular myocytes. / Al Kury, Lina T.; Voitychuk, Oleg I.; Yang, Keun Hang Susan; Thayyullathil, Faisal T.; Doroshenko, Petro; Ramez, Ali M.; Shuba, Yaroslav M.; Galadari, Sehamuddin; Howarth, Frank Christopher; Oz, Murat.

    In: British Journal of Pharmacology, Vol. 171, No. 14, 01.01.2014, p. 3485-3498.

    Research output: Contribution to journalArticle

    Al Kury, LT, Voitychuk, OI, Yang, KHS, Thayyullathil, FT, Doroshenko, P, Ramez, AM, Shuba, YM, Galadari, S, Howarth, FC & Oz, M 2014, 'Effects of the endogenous cannabinoid anandamide on voltage-dependent sodium and calcium channels in rat ventricular myocytes', British Journal of Pharmacology, vol. 171, no. 14, pp. 3485-3498. https://doi.org/10.1111/bph.12734
    Al Kury, Lina T. ; Voitychuk, Oleg I. ; Yang, Keun Hang Susan ; Thayyullathil, Faisal T. ; Doroshenko, Petro ; Ramez, Ali M. ; Shuba, Yaroslav M. ; Galadari, Sehamuddin ; Howarth, Frank Christopher ; Oz, Murat. / Effects of the endogenous cannabinoid anandamide on voltage-dependent sodium and calcium channels in rat ventricular myocytes. In: British Journal of Pharmacology. 2014 ; Vol. 171, No. 14. pp. 3485-3498.
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    abstract = "Background and Purpose The endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) exerts negative inotropic and antiarrhythmic effects in ventricular myocytes. Experimental Approach Whole-cell patch-clamp technique and radioligand-binding methods were used to analyse the effects of anandamide in rat ventricular myocytes. Key Results In the presence of 1-10 μM AEA, suppression of both Na+ and L-type Ca2+ channels was observed. Inhibition of Na+ channels was voltage and Pertussis toxin (PTX) - independent. Radioligand-binding studies indicated that specific binding of [3H] 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 Ca2+ 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 Ba2+ currents. MetAEA also inhibited Na+ and L-type Ca2+ currents. Radioligand studies indicated that specific binding of [3H]isradipine, was inhibited significantly by metAEA. (10 μM), changing Bmax but not Kd. Conclusion and Implications Results indicate that AEA inhibited the function of voltage-dependent Na+ and L-type Ca2+ channels in rat ventricular myocytes, independent of CB1 and CB2 receptor activation.",
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    T1 - Effects of the endogenous cannabinoid anandamide on voltage-dependent sodium and calcium channels in rat ventricular myocytes

    AU - Al Kury, Lina T.

    AU - Voitychuk, Oleg I.

    AU - Yang, Keun Hang Susan

    AU - Thayyullathil, Faisal T.

    AU - Doroshenko, Petro

    AU - Ramez, Ali M.

    AU - Shuba, Yaroslav M.

    AU - Galadari, Sehamuddin

    AU - Howarth, Frank Christopher

    AU - Oz, Murat

    PY - 2014/1/1

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    N2 - Background and Purpose The endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) exerts negative inotropic and antiarrhythmic effects in ventricular myocytes. Experimental Approach Whole-cell patch-clamp technique and radioligand-binding methods were used to analyse the effects of anandamide in rat ventricular myocytes. Key Results In the presence of 1-10 μM AEA, suppression of both Na+ and L-type Ca2+ channels was observed. Inhibition of Na+ channels was voltage and Pertussis toxin (PTX) - independent. Radioligand-binding studies indicated that specific binding of [3H] 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 Ca2+ 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 Ba2+ currents. MetAEA also inhibited Na+ and L-type Ca2+ currents. Radioligand studies indicated that specific binding of [3H]isradipine, was inhibited significantly by metAEA. (10 μM), changing Bmax but not Kd. Conclusion and Implications Results indicate that AEA inhibited the function of voltage-dependent Na+ and L-type Ca2+ channels in rat ventricular myocytes, independent of CB1 and CB2 receptor activation.

    AB - Background and Purpose The endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) exerts negative inotropic and antiarrhythmic effects in ventricular myocytes. Experimental Approach Whole-cell patch-clamp technique and radioligand-binding methods were used to analyse the effects of anandamide in rat ventricular myocytes. Key Results In the presence of 1-10 μM AEA, suppression of both Na+ and L-type Ca2+ channels was observed. Inhibition of Na+ channels was voltage and Pertussis toxin (PTX) - independent. Radioligand-binding studies indicated that specific binding of [3H] 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 Ca2+ 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 Ba2+ currents. MetAEA also inhibited Na+ and L-type Ca2+ currents. Radioligand studies indicated that specific binding of [3H]isradipine, was inhibited significantly by metAEA. (10 μM), changing Bmax but not Kd. Conclusion and Implications Results indicate that AEA inhibited the function of voltage-dependent Na+ and L-type Ca2+ channels in rat ventricular myocytes, independent of CB1 and CB2 receptor activation.

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