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Effects of the endogenous cannabinoid anandamide on voltage-dependent sodium and calcium channels in rat ventricular myocytes.
Br J Pharmacol. 2014 Jul; 171(14):3485-98.BJ

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 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 [(3) H]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 Ca(2+) channels in rat ventricular myocytes, independent of CB1 and CB2 receptor activation.

Authors+Show Affiliations

Laboratory of Functional Lipidomics, Department of Pharmacology, UAE University, Al Ain, UAE.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24758718

Citation

Al Kury, Lina T., et al. "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, 2014, pp. 3485-98.
Al Kury LT, Voitychuk OI, Yang KH, et al. Effects of the endogenous cannabinoid anandamide on voltage-dependent sodium and calcium channels in rat ventricular myocytes. Br J Pharmacol. 2014;171(14):3485-98.
Al Kury, L. T., Voitychuk, O. I., Yang, K. H., Thayyullathil, F. T., Doroshenko, P., Ramez, A. M., Shuba, Y. M., Galadari, S., Howarth, F. C., & 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), 3485-98. https://doi.org/10.1111/bph.12734
Al Kury LT, et al. Effects of the Endogenous Cannabinoid Anandamide On Voltage-dependent Sodium and Calcium Channels in Rat Ventricular Myocytes. Br J Pharmacol. 2014;171(14):3485-98. PubMed PMID: 24758718.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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 - 2013/09/25/received PY - 2014/02/17/revised PY - 2014/03/14/accepted PY - 2014/4/25/entrez PY - 2014/4/25/pubmed PY - 2015/4/22/medline KW - L-type Ca2+ channel KW - anandamide; Na+ channel KW - endocannabinoid KW - ventricular myocyte SP - 3485 EP - 98 JF - British journal of pharmacology JO - Br J Pharmacol VL - 171 IS - 14 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 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 [(3) H]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 Ca(2+) channels in rat ventricular myocytes, independent of CB1 and CB2 receptor activation. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/24758718/Effects_of_the_endogenous_cannabinoid_anandamide_on_voltage_dependent_sodium_and_calcium_channels_in_rat_ventricular_myocytes_ L2 - https://doi.org/10.1111/bph.12734 DB - PRIME DP - Unbound Medicine ER -