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Neuroprotectant minocycline depresses glutamatergic neurotransmission and Ca 2+ signalling in hippocampal neurons
Author(s) -
González José Carlos,
Egea Javier,
Del Carmen Godino María,
FernandezGomez Francisco J.,
SánchezPrieto José,
Gandía Luís,
García Antonio G.,
Jordán Joaquín,
HernándezGuijo Jesús M.
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05873.x
Subject(s) - excitatory postsynaptic potential , glutamatergic , minocycline , glutamate receptor , neuroprotection , postsynaptic potential , neurotransmission , neuroscience , chemistry , hippocampal formation , pharmacology , inhibitory postsynaptic potential , biology , biochemistry , receptor , antibiotics
The mechanism of the neuroprotective action of the tetracycline antibiotic minocycline against various neuron insults is controversial. In an attempt to clarify this mechanism, we have studied here its effects on various electrophysiological parameters, Ca 2+ signalling, and glutamate release, in primary cultures of rat hippocampal neurons, and in synaptosomes. Spontaneous excitatory postsynaptic currents and action potential firing were drastically decreased by minocycline at concentrations known to afford neuroprotection. The drug also blocked whole‐cell inward Na + currents ( I Na ) by 20%, and the whole‐cell Ca 2+ current ( I Ca ) by about 30%. Minocycline inhibited glutamate‐evoked elevation of the cytosolic Ca 2+ concentration ([Ca 2+ ] c ) by nearly 40%, and K + ‐evoked glutamate release from synaptosomes by 63%. Minocycline also depressed the frequency and amplitude of spontaneous excitatory postsynaptic currents, but did not affect the whole‐cell inward current elicited by γ‐aminobutyric acid or glutamate. This pharmacological profile suggests that the neuroprotective effects of minocycline might be associated with the mitigation of neuronal excitability, glutamate release, and Ca 2+ overloading.