Sodium channels (from rat, mouse, and man) in neuroblastoma cells and different expression systems have similar sensitivities to pentobarbital

Abstract

Current understanding of the molecular mechanisms of anaesthesia entails multiple molecular sites of anaesthetic action, each more or less important for a specific anaesthetic drug used. For some molecular anaesthetic targets such as the GABA A [4, 2], and acetylcholine receptors [5]as well as potassium channels [3], large differences in anaesthetic effects and sensitivity between different receptor subtypes have been found. Voltage-gated sodium channels have been shown to be affected at clinical concentrations of pentobarbital [12]. However, these results were obtained in an expression system, and anaesthetic sensitivity may be dependent on sodium channel subtype and subunit composition, too. Therefore, we compared the sensitivity of voltage-gated sodium channels to pentobarbital in human (SHSYSY) and mouse (N1E–115) neuroblastoma cell lines as well as an HEK293-cell expression system with previously reported data with other sodium channel subtypes. Remarkably, for all sodium channel subtypes studied as well as all subtypes reported in the literature, pentobarbital had qualitatively identical effects with some quantitative differences, and at potentials near the action potential threshold sodium currents were significantly reduced by clinical concentrations of pentobarbital.