Interactions of ethanol with single human brain sodium channels

• Published in: Neuroscience research communications 1997-03, Vol.20 (2), p.113-120
• Main Authors: Frenkel, C., Wartenberg, H.C., Rehberg, B., Urban, B.W.
• Format: Article
• Language: English
• Subjects: ethanol; general anaesthetic; human brain; lipid bilayer; mechanism of action; voltage-clamp
• ISSN: 0893-6609; 1520-6769
• DOI: 10.1002/(SICI)1520-6769(199703)20:2<113::AID-NRC192>3.0.CO;2-6

Human CNS sodium channels provide a protein model system for our continuing study of anaesthetic drug interactions at the molecular level. The impact of ethanol, an alcohol with general anaesthetic properties, on sodium channel function and their significance for the overall anaesthetic effect was quantified. Sodium channels from human brain cortex tissue were incorporated into voltage‐clamped planar lipid bilayers in the presence of batrachotoxin and studied at various ethanol concentrations (0.085 – 0.84 M). Ethanol caused a concentration‐dependent and membrane potential independent reduction of the single channel amplitude (major effect) and of the fractional channel open‐time (minor effect) with no effect on channel steady‐state activation. Severe membrane perturbing effects at the highest ethanol levels terminated the measurements. The weighted computer fit of the concentration‐response curve with an estimate of a maximal conductance block of 40% yielded an EC50 of 1.03 M. The EC50 for the 100% maximal theoretical block was calculated to be 3.3 M. These effects occurred at levels far beyond toxic human serum levels (0.1 M; 0.5%). Thus, the human CNS sodium channel is not a main target site for the clinical effects of ethanol and other, more sensitive central receptors are involved in ethanol's mechanism of action. © 1997 John Wiley & Sons, Ltd.