부산대학교 도서관

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 met AEA, 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. Met AEA also inhibited Na+ and L-type Ca2+ currents. Radioligand studies indicated that specific binding of [ 3H]isradipine, was inhibited significantly by met AEA. (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. [ABSTRACT FROM AUTHOR]