Abstract
The aim of the study was to explore the effects of memantine on responses elicited in the frog tectum by the bursts of spikes of moderate strength of a single retina ganglion cell and to gain an insight about the effect of memantine on the L-type Ca(2+) current. The experiments were performed in vivo on adult frogs (Rana temporaria). An individual retina ganglion cell (or its retinotectal fiber) was stimulated by current pulses delivered through a multichannel stimulating electrode positioned on the retina. Responses to the discharge of a single retinal ganglion cell were recorded in the tectum by an extracellular carbon-fiber microelectrode positioned in the terminal arborization of the retinotectal fiber in the tectum layer F. The solution of memantine (1-amino-3,5-dimethyladamantane) hydrochloride (30 or 45 μM) was applied onto the surface of the tectum by perfusion at a rate of 0.4 mL/min. Memantine (30-45 μM) largely inhibited the L-type Ca(2+) channel-mediated slow negative wave and late discharges seen in the tectum responses without any effect on fast synaptic retinotectal transmission. Our results suggest that the neuroprotective effect of memantine could arise not only through the inhibition of the NMDA receptor current but also through the suppression of the L-type Ca(2+) current.
Highlights
Memantine (1-amino-3,5-dimethyladamantane) shows clinical efficacy in patients with Alzheimer’s disease [1, 2]
Our results suggest that the neuroprotective effect of memantine could arise through the inhibition of the NMDA receptor current and through the suppression of the L-type Ca2+ current
30 μM of memantine was added to the perfusion solution, and a change in the amplitude and duration of the slow negative wave (sNW) and fast synaptic potentials (fSPs) was monitored during the perfusion when repeating the same stimulus (Figs. 1B and C)
Summary
Memantine (1-amino-3,5-dimethyladamantane) shows clinical efficacy in patients with Alzheimer’s disease [1, 2]. Most studies describe its neuroprotective effects through the inhibition of extrasynaptic NMDA receptors [3, 4]. Memantine seems to generate multiple other effects. It blocks α7 nicotinic acetylcholine [5] and 5-HT3 [6] receptors, stimulates cholinergic receptors [7], increases the production of kynurenic acid in the brain [8], inhibits ATP-dependent K+ conductance [9], depresses glutamate release [10], decreases the basal level of intracellular calcium [11], reduces the secretion of Alzheimer’s amyloid precursor protein and amyloid-β peptide [12], and relieves microgliaassociated inflammation and stimulates neurotrophic factor release from astroglia [13]. We have previously demonstrated that a discharge of action potentials of a single frog retina ganglion cell can evoke a long-lasting suprathreshold excitation of recurrent neurons of the tectum column [14] due to the activation of a slow dendritic L-type Ca2+ current seen in the recordings of tectal responses as
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