Neuroprotectant minocycline depresses glutamatergic neurotransmission and Ca(2+) signalling in hippocampal neurons

• Published in: The European journal of neuroscience 2007-11, Vol.26 (9), p.2481-2495
• Main Authors: González, José Carlos, Egea, Javier, Del Carmen Godino, María, Fernandez-Gomez, Francisco J, Sánchez-Prieto, José, Gandía, Luís, García, Antonio G, Jordán, Joaquín, Hernández-Guijo, Jesús M
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Anti-Bacterial Agents - pharmacology; Calcium - metabolism; Calcium Channels - drug effects; Calcium Channels - metabolism; Calcium Signaling - drug effects; Calcium Signaling - physiology; Cells, Cultured; Cytosol - drug effects; Cytosol - metabolism; Dose-Response Relationship, Drug; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Glutamic Acid - metabolism; Glutamic Acid - pharmacology; Hippocampus - drug effects; Hippocampus - metabolism; Male; Minocycline - pharmacology; Neurons - drug effects; Neurons - metabolism; Neuroprotective Agents - pharmacology; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, GABA - drug effects; Receptors, GABA - metabolism; Sodium Channels - drug effects; Sodium Channels - metabolism; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Synaptosomes
• ISSN: 0953-816X
• DOI: 10.1111/j.1460-9568.2007.05873.x

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 gamma-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.