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GABAmimetic intravenous anaesthetics inhibit spontaneous Ca 2+ ‐oscillations in cultured hippocampal neurons
Author(s) -
Sinner B.,
Friedrich O.,
Zink W.,
Fink R. H. A.,
Graf B. M.
Publication year - 2006
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.2006.01031.x
Subject(s) - hippocampal formation , bicuculline , gabaa receptor , biophysics , medicine , gamma aminobutyric acid , glutamate receptor , gaba receptor , gaba receptor antagonist , receptor , anesthesia , biology
Background: Spontaneous Ca 2+ ‐oscillations are a possible mechanism of Ca 2+ ‐mediated signal transduction in neurons. They develop by a periodical interplay of Ca 2+ , which enters the neuron from the extracellular medium and triggers Ca 2+ release from the endoplasmic reticulum (ER). Ca 2+ ‐oscillations are terminated by reuptake into the ER or plasmalemmal extrusion. Spontaneous Ca 2+ ‐oscillations are glutamate dependent and appear to be responsible for neuronal plasticity and integration of information. Here, we examined the role of the gamma‐aminobutyric acid (GABA A ) receptor on spontaneous Ca 2+ ‐oscillations and studied the effects of the anaesthetics midazolam, thiopental and the non‐anesthetic barbituric acid on spontaneous Ca 2+ ‐oscillations. Methods: Hippocampal neuronal cell cultures of 19‐day‐old embryonic Wistar rats 17–18 days in culture were loaded with the Ca 2+ ‐sensitive dye Fura‐2AM. Experiments were performed using dual wave‐length excitation fluorescence microscopy and calibration constants were obtained from in situ calibration. Results: Spontaneous Ca 2+ ‐oscillations are influenced by the GABA A receptor. The intravenous anaesthetics midazolam and thiopental suppressed the amplitude and frequency reversibly in a dose‐dependent manner with EC 50 in clinically relevant concentrations. This effect was mediated via the GABA A receptor as it could be reversed by the GABA A receptor antagonist bicuculline. In contrast, the application of barbituric acid had no effects on the spontaneous Ca 2+ ‐oscillations. Conclusion: Spontaneous Ca 2+ ‐oscillations are influenced by the GABA A receptor. Spontaneous Ca 2+ ‐oscillations might represent an interesting model system to study anaesthetic mechanisms on neuronal information processing.