Calcium channels control tDCS-induced spontaneous vesicle release from axon terminals

Abstract

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Molecular Insights into Transcranial Direct Current Stimulation Effects: Metabolomics and Transcriptomics Analyses

“…There is no current understanding of how an electrical current induces such metabolic effects. However, we also observed the effects of tDCS on calcium-related pathways, which coincides with previous studies by us and others [79,80,[85][86][87]. Calcium is known to modulate mitochondrial functioning [88][89][90], affecting ATP production [90] and regulating oxidative stress [91,92].…”

“…Given multiple hints that calcium signaling is involved in energy production processes that are affected by tDCS and given our previous study showing that tDCS modulates calcium dynamics [79,80], we investigated whether calcium-related genes were also altered by tDCS. We found that, as a whole, calcium-related genes are significantly affected by tDCS (Figure 9a).…”

The role of axonal voltage-gated potassium channels in tDCS

“…However, experimental data from recorded from axons show that polarization is higher than the theoretical predictions [14,15]. This disparity is due to the active involvement of ionic channels during the polarization process, such as the sodium channels and calcium channels, which were also shown to affect axonal polarization and synaptic vesicle release [15,39]. In the herein study, we demonstrate that along with the sodium channels and calcium channels, potassium channels also play a vital role in the modulation of synaptic vesicle release by DCS.…”

“…Ionic channel dynamics determines and regulates the waveform of the AP and a small variation in the axonal ionic channel dynamic can alter the AP morphology. Nonetheless, it is well established that the axon terminals are the most sensitive subcellular compartment to external electrical field application both by passive polarization in accordance with the cable equation [11,12,14,15], and by active involvement of ionic channels, which further enhances the polarization of the axon terminals [14,15,39]. Interestingly, the same ionic channels dynamics determine the initiation, waveform, and propagation of the APs [24,59].…”

Multi-scale model of axonal and dendritic polarization by transcranial direct current stimulation in realistic head geometry

“…Experiments in cortical and hippocampal slices found evidence of acute changes in synaptic efficacy that are strongest with E-field aligned with the activated axonal inputs [13,25]. Using slices from motor cortex, Vasu and Kaphzan reported changes in the rate of spontaneous vesicle release by dc stimulation, dependent on voltage-gated sodium, potassium, and calcium channels [61][62][63], suggesting modulation of presynaptic release machinery. However, electrophysiological measures of synaptic transmission include the influence of postsynaptic mechanisms, and the effects of dc stimulation on action potential-evoked presynaptic release have yet to be measured.…”