Abstract
Purpose: Remifentanil is known to cause vasodilation at standard anesthetic concentrations. The intracellular mechanisms underlying its vasodilator action may involve the activation of ion channels. The purpose of this study was to examine whether remifentanil inhibits L-type calcium channels (Ca.L) and provides dose-dependent effects on L-type calcium channel Ba2+ currents (IBa.L) in human mesenteric arterial smooth muscle cells.
Methods: Using the whole-cell patch-clamp method, an indepth analysis of the mechanism of the IBa.L induced by remifentanil was performed in cells which were enzymatically isolated from human mesenteric arterial smooth muscle. Ten millimolars Ba2+ was used to replace 1.5 mM Ca2+ to increase the amplitude of the inward current through Ca2+channels. L-type calcium channel Ba2+ was elicited during 50 msec depolarizing test pulses (150 msec duration) to +80 mV (10 mV increments) from a holding potential of −60 mV. The effects of remifentanil on Ca.L were observed at the following concentrations: 1.21, 4.84, and 19.4 nmol·L−1 and were compared with control.
Results: Remifentanil produced a concentration-dependent block of IBa,L with IC50 values of 38.90+-3.96×10−3 µmol·L−1. The L-type calcium channel blocker, nifedipine, antagonized these remifentanil-induced currents. Remifentanil, at all concentrations, shifted the maximum of the current-voltage relationship in the hyperpolarizing direction of IBa.L.
Conclusion: Remifentanil significantly inhibits Ca.L channels in a concentration-dependent manner in human mesenteric arteriolar smooth muscle cells.
Résumé
Objectif: Il est connu que le rémifentanil provoque une vasodilatation à des concentrations anesthésiques standard. Les mécanismes intracellulaires sous-jacents à son action vasodilatatrice pourrait impliquer l’activation des canaux ioniques. L’objectif de cette étude était de déterminer si le rémifentanil inhibe les canaux calciques de type L (CaL) et procure des effets dose-dépendants sur les courants Ba2+ des canaux calciques de type L (IBa.L) dans les cellules musculaires lisses des artères mésentériques humaines.
Méthode: À l’aide de la méthode « patch clamp » en configuration de cellule entière, une analyse approfondie du mécanisme du IBa.L provoqué par le rémifentanil a été réalisée sur des cellules isolées par action enzymatique du muscle lisse artériel mésentérique humain. Dix millimolaires Ba2+ ont été utilisés pour remplacer 1,5 mM Ca2+ afin d’augmenter l’amplitude du courant entrant à travers les canaux calciques. Le canal calcique de type L Ba2+ a été sollicité pendant des impulsions dépolarisantes de test de 50 msec (durée de 150 msec) jusqu’à + 80 mV (par paliers de 10 mV) à partir d’un potentiel de −60 mV. Les effets du rémifentanil sur le Ca.L ont été observés aux concentrations suivantes : 1,21, 4,84, et 19,4 nmol·L−1 et ont été comparés aux données du groupe témoin.
Résultats: Le rémifentanil a produit un bloc de IBa,L dépendant de la concentration avec des valeurs CI50 de 38,90±3,96×10−3 µmol·L−1. La nifédipine, un bloqueur des canaux calciques de type L, a opposé ces courants provoqués par le rémifentanil. Le rémifentanil, à toutes les concentrations évaluées, a déplacé le maximum de la relation courant-voltage dans la direction hyperpolarisante de IBa.L.
Conclusion: Le rémifentanil inhibe de manière significative les canaux calciques de type L (Ca.L) de fa?on dose-dépendante dans les cellules musculaires lisses de l’artère mésentérique humaine.
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This study was supported by grant No. 2005CB522601 from the 973 Program, Beijing, China, and grant No. 30271259 from the National Research Foundation of Nature Sciences. Beijing, China.
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Hu, ZY., Lin, PT., Liu, J. et al. Remifentanil induces l-type ca2+ channel inhibition in human mesenteric arterial smooth muscle cells. Can J Anesth 55, 238–244 (2008). https://doi.org/10.1007/BF03021508
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DOI: https://doi.org/10.1007/BF03021508