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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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

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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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