Сибаров Д. А.
Sibarov D.A.
Boikov S.I.
Stepanenko Y.D.
Karelina T.V.
Antonov S.M.

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Tricyclic antidepressants like amitriptyline (ATL) or desipramine (DES) are commonly used in the clinic. However, ATL and DES have multiple molecular targets, which complicates an explanation of their therapeutic effects. Recently we have shown ATL to enhance Ca2+ dependent desensitization of N-methyl-D-aspartate receptors (NMDAR) in clinically relevant concentrations (<10 μM) while direct channel block of NMDARs occurs at ten-fold higher levels.

Here in the model of primary culture of rat cortical neurons, we used Ca2+-sensitive dye and optical imaging to monitor intracellular Ca2+ responses of neurons to NMDA applications alone and in the presence of different ATL and DES concentrations.

We show that both ATL and DES inhibit NMDA elicited Ca2+ entry into neurons at therapeutic concentrations. We also report that ATL and DES can induce their Ca2+ responses, which depend on IP3-, but not ryanodine-dependent Ca2+ release from intracellular depots.

Thus, we describe here the modulation by tricyclic antidepressants of glutamate excitatory synaptic transmission and intracellular Ca2+ dynamics, which considerably interferes with many Ca2+-dependent mechanisms in neurons.

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