• 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, and Murat Oz.
• Laboratory of Functional Lipidomics, Department of Pharmacology, UAE University, Al Ain, UAE.
• Br. J. Pharmacol. 2014 Jul 1;171(14):3485-98.

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 [(3) H]isradipine, was inhibited significantly by metAEA. (10 μM), changing Bmax but not Kd .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.© 2014 The British Pharmacological Society.

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