Document Type
Article
Publication Date
2014
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.
Recommended 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 171.14 (2014): 3485-3498.
doi: 10.1111/bph.12734
Peer Reviewed
1
Copyright
Wiley
Included in
Animals Commons, Animal Structures Commons, Cardiovascular System Commons, Chemicals and Drugs Commons
Comments
This is the accepted version of the following article:
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 171.14 (2014): 3485-3498.
which has been published in final form at DOI: 10.1111/bph.12734.