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

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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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/