Objective: From the pathophysiological perspectives, Parkinson’s disease (PD) can be viewed as a prototypical disorder of “brain arrhythmias”. Therefore, the modulation of relevant ion channels by physical or chemical maneuvers may be important therapeutic considerations for PD. We describe a quantitative study investigating how the T-type Ca²⁺ channel (CaT) conductance influences the spike patterns in STN neurons.

Background: Deep brain stimulation (DBS) at the subthalamic nucleus (STN) has been a new and promising treatment of Parkinson’s disease (PD). STN neurons could discharge in the single-spike or the burst modes, but a significant increase in STN burst discharges has been documented in dopamine-deprived conditions such as PD.

Method: Here the interpretation of CaT ion channel is based on conventional Hodgkin-Huxley formalism. Then the CaT ion channel model is incorporated into a published STN electrophysiological model. A brief square pulse of varied duration and magnitude is applied as an external stimulus current (I_stim) to trigger action potential (AP) in the whole cell model. Then the CaT conductance and internal Ca²⁺ concentration Cai is varied to investigate the modulated response in AP and resting membrane potential.

Results: Voltage clamp protocol is used to generate CaT current for various test potentials in our model for validation. The electrical activities are generated in the whole cell model by applying a brief square pulse of varying magnitude (0.1-0.6nA) and duration (1-5ms). Then, we investigated the modulating effects of CaT current in two ways. First, we increased the CaT channel maximum conductance by 50% of its control value to get the promising effects in action potential. Then, we varied the Cai to observe the modulating effects in action potential. The opening of CaT channel enhanced the resting membrane potential from ─65mV to ─55mV before generation of the AP by the injected current in STN cell model.

Conclusion: The opening of CaT channel increased the resting membrane potential from ─65mV to ─55mV before generation of the action potential by the injected current in STN cell model. As the CaT channel openers depolarize the STN cell membrane by increasing Ca²⁺ ion permeability, reduce the initiation of spontaneous action potentials to bursting patterns, the pharmacological targeting of these channels may shed light on treatment of the PD.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/quantitative-study-of-t-type-ca2-channels-in-the-subthalamic-nucleus-neurons-towards-parkinsons-disease/