title: Enhancement by lanthanide of general anesthetic-induced GABAA-receptor current in rat septal cholinergic neurons in culture.
abstract: 1. Actions of lanthanide ions were examined on general anesthetic-induced currents mediated by the activation of gamma-aminobutyric acid-A receptors (GABAARs) in rat septal cholinergic neurons in primary culture, by means of a whole cell voltage-clamp technique. 2. La3+ enhanced a pentobarbital sodium (500 microM)-induced GABAAR current in a reversible and dose-dependent manner (median effective concentration = 15.7 microM; Hill coefficient = 1.58; 89% increase by 100 microM La3+). This action was independent of holding potentials (-34-26 mV), and was due to an increase in the apparent affinity for pentobarbital (295% increase with 100 microM La3+). 3. The action of La3+ on pentobarbital current was mimicked particularly by other lanthanide ions (Ce3+, Nd3+, Gd3+, Tb3+, Er3+, and Yb3+) and by Y3+ among a number of multivalent cations. There was no correlation between the potentiated proportions by lanthanide ions and their crystal ionic radii. 4. La3+ (100 microM) also augmented a GABAAR response evoked by either alpha-chloralose (500 microM), 2,6-diisopropylphenol (50 microM), or 3-alpha-hydroxy-5-alpha-pregnane-11,20-dione (20 microM) (144, 80, and 153% increase, respectively). 5. We suggest that the GABAAR channels on septal neurons are endowed with a novel "lanthanide site" whose activation results in a positive allosteric interaction with a binding site of the general anesthetics that is involved in a direct activation of GABAAR channels without any added exogenous GABA.
authors.affiliation: Department of Physiology, Saga Medical School, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Kumamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Murata
mesh_terms: D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002478:Cells, Cultured; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism*; D058785:GABA-A Receptor Agonists; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007811:Lanthanum / Q000494:pharmacology; D008674:Metals, Rare Earth / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats
chemical_list: D000759:Adjuvants, Anesthesia; D018681:Anesthetics, General; D058785:GABA-A Receptor Agonists; D007473:Ion Channels; D008674:Metals, Rare Earth; D007811:Lanthanum; D010424:Pentobarbital