Inhibition of dendritic L-type calcium current by memantine in frog tectum.

UNLABELLED: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Distinctive neurophysiological properties of embryonic trigeminal and geniculate neurons in culture.

Neurons in trigeminal and geniculate ganglia extend neurites that share contiguous target tissue fields in the fungiform papillae and taste buds of the mammalian tongue and thereby have principal roles in lingual somatosensation and gustation. Although functional differentiation of these neurons is central to formation of lingual sensory circuits, there is little known about electrophysiological properties of developing trigeminal and geniculate ganglia or the extrinsic factors that might regulate neural development. We used whole cell recordings from embryonic day 16 rat ganglia, maintained in culture as explants for 3-10 days with neurotrophin support to characterize basic properties of trigeminal and geniculate neurons over time in vitro and in comparison to each other. Each ganglion was cultured with the neurotrophin that supports maximal neuron survival and that would be encountered by growing neurites at highest concentration in target fields. Resting membrane potential and time constant did not alter over days in culture, whereas membrane resistance decreased and capacitance increased in association with small increases in trigeminal and geniculate soma size. Small gradual differences in action potential properties were observed for both ganglion types, including an increase in threshold current to elicit an action potential and a decrease in duration and increase in rise and fall slopes so that action potentials became shorter and sharper with time in culture. Using a period of 5-8 days in culture when neural properties are generally stable, we compared trigeminal and geniculate ganglia and revealed major differences between these embryonic ganglia in passive membrane and action potential characteristics. Geniculate neurons had lower resting membrane potential and higher input resistance and smaller, shorter, and sharper action potentials with lower thresholds than trigeminal neurons. Whereas all trigeminal neurons produced a single action potential at threshold depolarization, 35% of geniculate neurons fired repetitively. Furthermore, all trigeminal neurons produced TTX-resistant action potentials, but geniculate action potentials were abolished in the presence of low concentrations of TTX. Both trigeminal and geniculate neurons had inflections on the falling phase of the action potential that were reduced in the presence of various pharmacological blockers of calcium channel activation. Use of nifedipine, omega-conotoxin-MVIIA and GVIA, and omega-agatoxin-TK indicated that currents through L-, N-, and P/Q- type calcium channels participate in the action potential inflection in embryonic trigeminal and geniculate neurons. The data on passive membrane, action potential, and ion channel characteristics demonstrate clear differences between trigeminal and geniculate ganglion neurons at an embryonic stage when target tissues are innervated but receptor organs have not developed or are still immature. Therefore these electrophysiological distinctions between embryonic ganglia are present before neural activity from differentiated receptive fields can influence functional phenotype.