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The parkinsonian neurotoxin, 1-methyl-4-phenyl pyridinium (MPP+), affects voltage activated calcium channels in DRG neurons

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Title The parkinsonian neurotoxin, 1-methyl-4-phenyl
pyridinium (MPP+), affects voltage activated calcium
channels in DRG neurons
 
Creator Chandra, G
Bu¨ sselberg, D
Mohanakumar, K P
 
Subject Cell Biology & Physiology
 
Description Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes
parkinsonian syndromes in human and animals, which is featured by hypoactivity
of dopamine (DA) neurotransmitter system resulting from degeneration of
dopaminergic neurons of substantia nigra pars compacta (SNpc) region of the
brain. NMDA receptor-mediated cell death, altered intracellular Ca2+ homeostasis,
and functional run-down of ligand-gated (GABAA) channels of dopaminergic cells
are some propositions that point to an active involvement of membrane
depolarization as an initial event in MPTP-neurotoxicity. In the present study,
we reported the effects of MPTP and and its active neurotoxic metabolite,
1-methyl-4-phenyl pyridinium ion (MPP+) on voltage-activated inward currents of
cultured dorsal root ganglia (DRG) neurons derived from neonatal rats. Voltageactivated
Ca2+, K+ and Na+ currents were elicited in the whole-cell configuration
of the patch clamp technique, and were isolated using specific internal solutions.
Externally applied MPTP and MPP+ showed opposing effects on the electrical
properties of DRG neurons and only MPP+ showed significant inhibitory effects.
Voltage-activated Ca2+ currents were dose- and time-dependently inhibited by
MPP+, while higher doses of MPP+ evoked an inhibitory effect on the voltagegated
K+ currents. The voltage-activated Na+ currents remained unaltered. The
present study indicates that, MPP+ reduces currents through voltage-gated Ca2+
channels, and this may have direct bearing on the neurotoxicity caused by this
potent neurotoxin.
 
Date 2003
 
Type Conference or Workshop Item
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1077/1/3_4_JN_2003.pdf
Chandra, G and Bu¨ sselberg, D and Mohanakumar, K P (2003) The parkinsonian neurotoxin, 1-methyl-4-phenyl pyridinium (MPP+), affects voltage activated calcium channels in DRG neurons. In: Joint Meeting of the International-Society-for-Neurochemistry/Asian-Pacific-Society-for-Neurochemistry, WANCHAI, PEOPLES R CHINA.
 
Relation http://onlinelibrary.wiley.com/doi/10.1046/j.1474-1644.2003.2175_9.x/pdf
http://www.eprints.iicb.res.in/1077/