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J Neurophysiol 75: 2294-2299, 1996;
0022-3077/96 $5.00
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Journal of Neurophysiology, Vol 75, Issue 6 2294-2299, Copyright © 1996 by APS

ARTICLES

Enhancement by lanthanide of general anesthetic-induced GABAA-receptor current in rat septal cholinergic neurons in culture

E. Kumamoto and Y. Murata
Department of Physiology, Saga Medical School, Japan.

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.


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