6-OHDA induced calcium influx through N-type calcium channel alters membrane properties via PKA pathway in substantia nigra pars compacta dopaminergic neurons

• 6-OHDA could alter membrane properties in SNc DA neurons.
• Cav2.2 may be involved in the 6-OHDA-induced oxidative stress.
• PKA plays a key role on 6-OHDA-induced Ca2+ entry.

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 (0.5–2 mM) evoked a dose-dependent, desensitizing inward current and intracellular free calcium concentration ([Ca2+]i) rise. In voltage clamp, ω-conotoxin-sensitive Ca2+ current modulation mediated by 6-OHDA reflected an altered sensitivity. Furthermore, we found that 6-OHDA modulated Ca2+ 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).