The Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on membrane currents and intrasynaptosomal calcium

K. P. Mohanakumar, S. Samanta Ray, D. Büsselberg

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Abstract

Effects of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite, 1-methyl-4-phenyl pyridinium (MPP+) were investigated on neuronal membrane currents and intrasynaptosomal calcium levels employing whole cell patch clamp and FURA-2AM respectively. Membrane currents elicited by voltage ramps as well as voltage activated potassium-currents were studied in the cultured rat dorsal root ganglia (DRG) neurons. These neurons contained 0.36 ± 0.04 pmol/mg of dopamine as detected employing HPLC-electrochemistry. MPTP and MPP+ (1μM) respectively caused significant increase (25 ± 4%) or inhibition (53 ± 10%) of the total membrane current. Potassium-currents elicited by voltage jumps from -80 to 0 mV were significantly inhibited (68 ± 8%) by MPP+, but MPTP caused no effect. MP+-induced increase in the FURA-2 fluorescence signal was insensitive to extrasynaptosomal calcium, indicated intrasynaptosomal mobilization by the neurotoxin. These results suggest involvement of ion channels in MPTP neurotoxicity, and imply its role in the etiopathology of Parkinson's disease.

Original languageEnglish
Pages (from-to)35-42
Number of pages8
JournalNeuroscience Research Communications
Volume30
Issue number1
DOIs
Publication statusPublished - 26 Mar 2002

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Keywords

  • Dopamine, MPP
  • Neurotoxicity
  • Patch-clamp studies
  • Voltage activated K-currents

ASJC Scopus subject areas

  • Neuroscience(all)

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