Magnetic Fields and Magnetically Stimulated Gold-Coated Superparamagnetic Iron Oxide Nanoparticles Differentially Modulate L-Type Voltage-Gated Calcium Channel Activity in Midbrain Neurons

Abstract

Nanoparticles (NPs) generate localized magnetic forces during magnetic stimulation, which can, in turn, modulate neuronal excitability and regulate downstream signaling in neurons. In agreement with this idea, under static magnetic field stimulation (SMS), gold-coated superparamagnetic iron oxide (Au-SPIO) core–shell nanoparticles (NPs) can promote and guide the direction of neurite outgrowth. Inspired by these promising results, this study investigates how SMS on Au-SPIO (SMS-Au-SPIO) affects the physiology of midbrain neurons. Transmission electron microscopy (TEM) images showed quasispherical shapes and a diameter of 20 ± 4 nm of Au-SPIO NPs synthesized by forming an Au layer on SPIO using a hydroxylamine hydrochloride-assisted seed growth method. We found that SMS enhanced intracellular uptake of Au-SPIO and that SMS-Au-SPIO resulted in a delayed blockade of an L-type voltage-gated Ca2+ channel (VGCC) in midbrain neurons. Specifically, the frequency of spontaneous L-type VGCC-induced Ca2+ fluxes was significantly reduced in midbrain neurons exposed to either SMS or Au-SPIO or SMS-Au-SPIO. A power spectrum density analysis of Ca2+ fluxes showed that SMS decreased Ca2+ fluxes amplitudes (<0.1 Hz) before and after L-type VGCC blockade. By contrast, SMS-Au-SPIO decreased Ca2+ flux amplitudes only after L-type VGCC blockade, suggesting a modulation of L-type VGCC by SMS-Au-SPIO. Finally, while SMS alone induced apoptosis of dopaminergic (DA) neurons, SMS-Au-SPIO did not. Thus, SMS and SMS-Au-SPIO differentially modulate L-type VGCC-mediated Ca2+ fluxes, and downstream apoptotic signaling in midbrain neurons, implying the possible application of SMS-Au-SPIO as a drug delivery strategy to treat Parkinson’s disease.