Objective: Parkinson’s disease (PD) might be seen as a classic manifestation of “brain arrhythmias” from a pathological standpoint. This work aims to examine the impact of T-type Ca2+ channel (CaT) conductance on spike patterns in Subthalamic nucleus (STN) neurons through a quantitative approach.

Background: The STN deep brain stimulation (DBS) has emerged as a novel and auspicious therapeutic approach for PD.

Method: The CaT ion channel is interpreted using the usual Hodgkin-Huxley formalism. The CaT ion channel model is subsequently integrated into a previously published electrophysiological model of the STN. An external stimulus current (Istim) is applied as a short square pulse with varying length and magnitude to initiate an action potential (AP) in the entire cell model. In order to examine the modulated response in AP and resting membrane potential, the CaT conductance and internal Ca2+ concentration Cai are manipulated.

Results: The voltage clamp methodology is employed to produce CaT current within our model for validation, at different test potentials. The electrical activities throughout the entire cell model are produced through the application of a short square pulse with variable magnitudes (ranging from 0.2 to 0.4 nA) and durations (ranging from 2 to 4ms). Next, we examined the modifying impacts of CaT current using two distinct methods. Initially, we augmented the maximal conductance of the CaT channel by 50% of its control value to achieve favorable outcomes in terms of action potential. Subsequently, the Cai was manipulated to examine the modulatory effects on the action potential. In the STN cell model, the activation of the CaT channel resulted in an increase in the resting membrane potential from – 60mV to -54mV before the formation of the AP by the injected current.

Conclusion: By increasing the permeability of Ca2+ ions, CaT channel openers depolarize the STN cell membrane and diminish the start of spontaneous action potentials to burst patterns. Targeting these channels pharmacologically may provide insights into the therapy of Parkinson’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/investigation-of-the-quantitative-impact-of-t-type-calcium-channels-in-subthalamic-nucleus-neurons-on-parkinsons-disease/