Effects of the endogenous cannabinoid anandamide on voltage-dependent sodium and calcium channels in rat ventricular myocytes.
Br J Pharmacol
; 171(14): 3485-98, 2014 Jul.
Article
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| MEDLINE
| ID: mdl-24758718
ABSTRACT
BACKGROUND AND PURPOSE:
The endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) exerts negative inotropic and antiarrhythmic effects in ventricular myocytes. EXPERIMENTALAPPROACH:
Whole-cell patch-clamp technique and radioligand-binding methods were used to analyse the effects of anandamide in rat ventricular myocytes. KEYRESULTS:
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.Palabras clave
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Banco de datos:
MEDLINE
Asunto principal:
Cannabinoides
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Bloqueadores de los Canales de Calcio
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Ácidos Araquidónicos
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Bloqueadores de los Canales de Sodio
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Miocitos Cardíacos
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Endocannabinoides
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Alcamidas Poliinsaturadas
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Ventrículos Cardíacos
Límite:
Animals
Idioma:
En
Año:
2014
Tipo del documento:
Article