Abstract
Purpose
N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex (PFC) are closely related with the excitability of pyramidal neurons and PFC function. As the effect of thiopental sodium on the central nervous system may partly result from the inhibition of PFC NMDA receptors, we investigated the effect of thiopental sodium with different concentrations on NMDA-gated currents in acutely dissociated rat PFC pyramidal neurons. We sought to determine whether thiopental sodium inhibits NMDA receptor function.
Methods
Three to four week old male Sprague-Dawley rats were sacrificed and the PFC was dissected. Pyramidal neurons from the PFC were prepared and standard whole-cell patch clamp recordings were performed. Escalating concentrations from 3-1000 μM NMDA were applied 100 μm from the pyramidal cells, and the concentration in the effect compartment related to 50% effect (EC50) of NMDA was determined for the ensuing experiments. One hundred μM NMDA alone (control) or NMDA with different concentrations (10-1000 μM) of thiopental sodium were applied. After the inhibitory concentration, in 50% of NMDA effect (IC50) of thiopental sodium was established this IC50 and NMDA 3-1000 μM were applied 100 μm from the pyramidal cells. The EC50 value of NMDA under the effect of IC50 thiopental sodium was determined.
Results
N-methyl-D-aspartate induced inward currents in a concentration-dependent manner, which were completely antagonized by 50 μM AP5. The maximal amplitude of NMDA-induced current was 1.15 ± 0.27 nA. The EC50 of NMDA was 53.6 ± 12.4 μM. The NMDA (100 μM)-gated current was inhibited by thiopental sodium in a concentration-dependent manner, and the IC50 of thiopental sodium was 33.6 ± 6.1 μM. Under the effect of 33.6 μM thiopental sodium, the maximal amplitude of NMDA-induced current was 0.87 ± 0.17 nA. The concentration-response curve of NMDA was shifted rightwards. The EC50 of NMDA was 128 ± 15 μM, which was greater than that of NMDA without thiopental sodium (P < 0.01).
Conclusions
Thiopental sodium decreases NMDA-gated currents in acutely dissociated rat prefrontal cortical pyramidal neurons in a concentration-dependent manner.
Résumé
Objectif
Les récepteurs de N-méthyl-D-aspartate (NMDA) dans le cortex préfrontal (CPF) sont en lien étroit avec ľexcitabilité des neurones pyramidaux et la fonction du CPF. ľeffet du thiopental sodique sur le système nerveux central pouvant résulter de ľinhibition des récepteurs de NMDA du CPF, nous recherchons ľeffet de différentes concentrations de thiopental sodique sur les récepteurs NMDA dans des neurones pyramidaux très dissociés du CPF de rat. Nous voulons savoir si le thiopental sodique inhibe la fonction des récepteurs de NMDA.
Méthode
Des rats mâles Sprague-Dawley, de trois à quatre semaines, ont été sacrifiés et le CPF disséqué. Les neurones pyramidaux du CPF ont été préparés et des enregistrements standards selon la technique «patch clamp» ont été réalisés. Des concentrations croissantes de 3-1000 μM de NMDA ont été appliquées à 100 μm des cellules pyramidales et la concentration dans le compartiment effecteur, reliée à 50 % ďeffet (EC50) de NMDA, a été déterminée pour les expériences ultérieures. Cent μM de NMDA seul (témoin) ou du NMDA avec différentes concentrations (10-1000 μM) de thiopental sodique ont été appliqués. Après ľétablissement de la concentration inhibitrice de thiopental sodique chez 50 % ďeffet de NMDA, cette IC50 et 3-1000 μM de NMDA ont été appliqués à 100 μm des cellules pyramidales. ľEC50 de NMDA sous ľeffet de IC50 de thiopental sodique a été déterminé.
Résultats
Le N-méthyl-D-aspartate a induit des courants entrants, en fonction de la concentration, qui ont été complètement antagonisés par 50 μM ďAP5. ľamplitude maximale du courant induit par le NMDA a été de 1,15 ± 0,27 nA. ľEC50 du NMDA a été de 53,6 ± 12,4 μM. Le courant contrôlé par le NMDA (100 μM) a été inhibé par le thiopental sodique en fonction de la concentration et ľIC50 du thiopental sodique a été de 33,6 ± 6,1 μM. Sous ľeffet de 33,6 μM de thiopental sodique, ľamplitude maximale du courant induit par le NMDA a été de 0,87 ± 0,17 nA. La courbe de concentration-réponse du NMDA a été déplacée vers la droite. ľEC50 du NMDA a été de 128 ± 15 μM, ce qui est plus important que celui du NMDA sans le thiopental sodique (P < 0,01).
Conclusion
Le thiopental sodique a diminué, en fonction de la concentration, les courants contrôlés par le NMDA dans des neurones pyramidaux très dissociés de cortex préfrontal de rat.
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Liu, H., Dai, T. & Yao, S. Effect of thiopental sodium on N-methyl-D-aspartate-gated currents. Can J Anesth 53, 442–448 (2006). https://doi.org/10.1007/BF03022615
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DOI: https://doi.org/10.1007/BF03022615