title: 6-OHDA induced calcium influx through N-type calcium channel alters membrane properties via PKA pathway in substantia nigra pars compacta dopaminergic neurons.
abstract: Voltage gated calcium channels (VGCC) are sensitive to oxidative stress, and their activation or inactivation can impact cell death. Although these channels have been extensively studied in expression systems, their role in the brain, particularly in the substantia nigra pars compacta (SNc), remain controversial. In this study, we assessed 6-hydroxydopamine (6-OHDA) induced transformation of firing pattern and functional changes of calcium channels in SNc dopaminergic neurons. Application of 6-OHDA (0.5-2mM) evoked a dose-dependent, desensitizing inward current and intracellular free calcium concentration ([Ca(2+)]i) rise. In voltage clamp, ω-conotoxin-sensitive Ca(2+) current modulation mediated by 6-OHDA reflected an altered sensitivity. Furthermore, we found that 6-OHDA modulated Ca(2+) currents through PKA pathway. These results provided evidence for the potential role of VGCCs and PKA involved in oxidative stress in degeneration of SNc neurons in Parkinson's disease (PD).
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, Shaanxi, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, Shaanxi, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, Shaanxi, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, Shaanxi, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, Shaanxi, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, Shaanxi, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, Shaanxi, China. Electronic address: gguodong@fmmu.edu.cn.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, Shaanxi, China. Electronic address: xuelianwang3@126.com.
authors.forename: Xue-Lian
authors.initials: XL
authors.lastname: Wang
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D018384:Oxidative Stress; D016627:Oxidopamine / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D024642:Potassium Channels, Voltage-Gated; D016627:Oxidopamine; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium
keywords: 6-OHDA; Dopaminergic neuron; N-type calcium channel; Substantia Nigra pars compacta (SNc); cAMP-Dependent protein kinase (PKA)