Objective: The pathogenesis of Parkinson’s Disease (PD) is associated with electrical firing patterns of the subthalamic nucleus (STN) neuronal cells. As the dysfunction of the active ion channels across the membrane generates abnormal firing patterns, PD is also known as an ion channel dysfunction disease. Here, the aim is to investigate the effect of drugs on calcium channels in modulating the electrical activities of the STN cells.

Background: The intracellular electrical firing patterns of the STN cells are related to major neurodegenerative disorders, where PD is closely associated with it. In the last decades, it has been shown that deep brain stimulation (DBS) at the STN site is a promising invasive treatment for PD.

Method: The in silico electrophysiological setup for an isolated STN cell is established. The electrical equivalent model of the single isolated STN cell comprises all active ion channels. pumps, and exchangers across the cell membrane. A drug model for both voltage-gated T – type and L- type Ca2+ channels is introduced by varying the ion channel maximum conductance for the respective ion channels.

Results: Under the voltage clamp protocol, the individual current for both T – type and L- type Ca2+ channels are recorded. Then antagonists of the T – type, and L- type Ca2+ channels are applied by reducing the individual ion channel maximum conductance. The ion channels are incorporated and the firing patterns are generated by injecting a step current stimulus intracellularly. It shows the resting membrane potential (RMP) at ─50 mV and the action potentials (AP) are generated in the single spike mode pattern. The STN neurons fire burst mode firing patterns when the RMP is reduced to ─65 mV. The inhibition of the L-type Ca2+ channel abolishes the burst mode firing patterns and the inhibition of the T-type Ca2+ channel abolishes the slope of the burst plateau in the AP rising phase.

Conclusion: The dysfunction of neuronal voltage-gated calcium ion channels has been associated with neurodegeneration in PD. The role of T-type and L-type Ca2+ currents in the genesis of STN neuron burst discharges are demonstrated in our study. Our results support the proper dosing of T-type and L-type calcium channel inhibitors as alternate non-dopaminergic pharmacological targets for PD to overcome high-dose levodopa therapy.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/in-silico-electrophysiology-study-reveals-the-modulating-role-of-calcium-channel-on-subthalamic-nucleus-neuronal-cells-towards-parkinsons-disease/