Actions of the sodium channel inhibitor 202W92 on rat midbrain dopaminergic neurons

Luigi Caputi, Atticus Hainsworth, Ezia Guatteo, Alessandro Tozzi, Alessandro Stefani, Francesca Spadoni, Michael Leach, Giorgio Bernardi, Nicola B. Mercuri

Research output: Contribution to journalArticle

Abstract

Excessive glutamatergic activity is implicated in Parkinson's disease (PD) and sodium channel blockade, resulting in inhibition of glutamate release, is a potential therapeutic approach to PD therapy. Beneficial effects of riluzole and lamotrigine have been reported in animal models of PD, but these compounds have relatively low potency as sodium channel inhibitors and also inhibit N and P/Q-type calcium channels. 202W92, a structural analog of lamotrigine, is a potent sodium channel inhibitor, with no effect on N, P/Q-type channels. Here we present the effects of 202W92 on single patch-clamped dopaminergic neurons. 202W92 (≥10 μM) inhibited spontaneous action potential firing and reduced amplitude and frequency of evoked action potentials. It also inhibited the frequency of 4-aminopyridine (4-AP)- and electrically evoked excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs), with >80% inhibition at 10 μM (IC 50 1.5 μM). EPSC and IPSC amplitudes were partially inhibited. 202W92 did not affect postsynaptic responses to locally applied glutamate and GABA, nor spontaneously occurring mini-IPSCs. These actions of 202W92 are compatible with sodium channel inhibition and depression of transmitter release.

Original languageEnglish
Pages (from-to)123-130
Number of pages8
JournalSynapse
Volume48
Issue number3
DOIs
Publication statusPublished - Jun 1 2003

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Sodium Channel Blockers
Inhibitory Postsynaptic Potentials
Dopaminergic Neurons
Mesencephalon
Parkinson Disease
Sodium Channels
Excitatory Postsynaptic Potentials
Action Potentials
Glutamic Acid
Q-Type Calcium Channels
P-Type Calcium Channels
Riluzole
4-Aminopyridine
Evoked Potentials
gamma-Aminobutyric Acid
Animal Models
Therapeutics
lamotrigine

Keywords

  • Firing discharge
  • Neuroprotection
  • Parkinson's disease
  • Sodium influx
  • Synaptic transmission

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

Cite this

Actions of the sodium channel inhibitor 202W92 on rat midbrain dopaminergic neurons. / Caputi, Luigi; Hainsworth, Atticus; Guatteo, Ezia; Tozzi, Alessandro; Stefani, Alessandro; Spadoni, Francesca; Leach, Michael; Bernardi, Giorgio; Mercuri, Nicola B.

In: Synapse, Vol. 48, No. 3, 01.06.2003, p. 123-130.

Research output: Contribution to journalArticle

Caputi, L, Hainsworth, A, Guatteo, E, Tozzi, A, Stefani, A, Spadoni, F, Leach, M, Bernardi, G & Mercuri, NB 2003, 'Actions of the sodium channel inhibitor 202W92 on rat midbrain dopaminergic neurons', Synapse, vol. 48, no. 3, pp. 123-130. https://doi.org/10.1002/syn.10195
Caputi L, Hainsworth A, Guatteo E, Tozzi A, Stefani A, Spadoni F et al. Actions of the sodium channel inhibitor 202W92 on rat midbrain dopaminergic neurons. Synapse. 2003 Jun 1;48(3):123-130. https://doi.org/10.1002/syn.10195
Caputi, Luigi ; Hainsworth, Atticus ; Guatteo, Ezia ; Tozzi, Alessandro ; Stefani, Alessandro ; Spadoni, Francesca ; Leach, Michael ; Bernardi, Giorgio ; Mercuri, Nicola B. / Actions of the sodium channel inhibitor 202W92 on rat midbrain dopaminergic neurons. In: Synapse. 2003 ; Vol. 48, No. 3. pp. 123-130.
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