Changes of action potential and L-type calcium channel current of Sprague-Dawley rat ventricular myocytes by different amlodipine isomers

Authors: Jiang, Wen-ping; Wang, Ru-xing

Source: Canadian Journal of Physiology and Pharmacology, Volume 86, Number 9, September 2008 , pp. 620-625(6)

Publisher: NRC Research Press

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Abstract:

To investigate the effects of S- and R-amlodipine (Aml) on action potential (AP) and L-type calcium channel current (ICa-L), the whole-cell patch-clamp technique was used on rat ventricular myocytes to record AP, ICa-L, peak currents, steady-state activation currents, steady-state inactivation currents, and recovery currents from inactivation with S-Aml and R-Aml at various concentrations. Increasing concentrations of S-Aml gradually shortened AP durations (APDs). At concentrations of 0.1, 0.5, 1, 5, and 10 mol/L, S-Aml blocked 1.5% ± 0.2%, 25.4% ± 5.3%, 65.2% ± 7.3%, 78.4% ± 8.1%, and 94.2% ± 5.0% of ICa-L, respectively (p < 0.05), and the half-inhibited concentration was 0.62 ± 0.12 µmol/L. Current-voltage curves were shifted upward; steady-state activation and inactivation curves were shifted to the left. At these concentrations of S-Aml, the half-activation voltages were -16.01 ± 1.65, -17.61 ± 1.60, -20.17 ± 1.46, -21.87 ± 1.69, and -24.09 ± 1.87 mV, respectively, and the slope factors were increased (p < 0.05). The half-inactivation voltages were -27.16 ± 4.48, -28.69 ± 4.52, -31.19 ± 4.17, -32.63 ± 4.34, and -35.16 ± 4.46 mV, respectively, and the slope factors were increased (p < 0.05). The recovery times from inactivation of S-Aml were prolonged (p < 0.05). In contrast, R-Aml had no effect on AP and ICa-L (p > 0.05) at the concentrations tested. Thus, only S-Aml has calcium channel blockade activity, whereas R-Aml has none of the pharmacologic actions associated with calcium channel blockers.

Cette étude se propose d’analyser l’effet de l’amlodipine (S, R) (Aml) sur le potentiel d’action (AP) et sur le courant des canaux calciques de type L (ICa-L), chez des myocytes ventriculaires de rat. Après l’inactivation des cellules S-Aml et R-Aml administrées à diverses concentrations, on enregistre les variables suivantes au moyen de la technique du patch clamp: le potentiel d’action, le courant des canaux calciques de type L, les courants de pointe, les courants d’activation en régime stable, les courants d’inactivation en régime stable et les courants de récupération. La durée des potentiels d’action (APDs) est abrégée graduellement en fonction des concentrations de S-Aml : 0,1, 0,5, 1, 5, et 10 mol/L (p < 0,05). 1,5 % ± 0,2 %, 25,4 % ± 5,3 %, 65,2 % ± 7,3 %, 78,4 % ± 8,1 %, et 94,2 % ± 5,0 % du courant calcique est bloqué par S-Aml et la concentration de demi-inhibition est égale à 0,62 ± 0,12 µmol/L. Les courbes I-V sont déplacées vers le haut ; les courbes d’activation et d’inactivation en régime stable sont déplacées vers la gauche. Les potentiels de demi-activation sont -16,01 ± 1,65, -17,61 ± 1,60, -20,17 ± 1,46, -21,87 ± 1,69, et -24,09 ± 1,87 mV et les coefficients de la pente augmentent (p < 0,05). Les potentiels de demi-inactivation sont -27,16 ± 4,48, -28,69 ± 4,52, -31,19 ± 4,17, -32,63 ± 4,34, et -35,16 ± 4,46 mV et les coefficients de la pente augmentent (p < 0,05). Les délais de récupération après l’inactivation par S-Aml sont prolongés (p < 0,05). Néanmoins, on n’observe aucun effet de R-Aml sur AP et sur ICa-L, quelles que soient les concentrations (p > 0,05). Seulement S-Aml peut entraver l’activité du canal calcique ; R-Aml n’a aucun des pouvoirs pharmacologiques associés aux inhibiteurs calciques.

Document Type: Research Article

Publication date: September 1, 2008

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