Objective: This study describes the role of the subthalamic ERG Potassium (ERG K+) ion channel conductance in cellular excitability in subthalamic nucleus (STN) neurons towards Parkinson’s disease (PD).

Background: It has been observed that deep brain stimulation (DBS) at the STN neuron site improves the PD as a new effective treatment method. The firing properties of STN neurons in terms of single-spike or the burst modes modulate pathophysiological conditions in PD. ERG Potassium channel play dominant role in regulating firing properties of STN neurons.

Method: Here the interpretation of ERG K+ ion channel is based on conventional Hodgkin-Huxley formalism. Then the ERG K+ ion channel model is incorporated into a published STN electrophysiological model in Gillies et al., 2006. A brief square pulse of varied duration and magnitude is applied as an external stimulus current (Istim) to trigger action potential (AP) in the whole cell model.

Results: Voltage clamp protocol is used to generate ERG K+ current for various test potentials and the results are validated against experimental data in Huang et al., 2017. The electrical activities are generated in the whole cell model by applying a brief square pulse of varying magnitude (0.1-0.6 nA) and duration (1-5ms). Then, we investigated the modulating effects of ERG K+ current by altering the maximum conductance. The opening of ERG K+ channel reduced the resting membrane potential from ─65 mV to ─70 mV before generation of the AP by the injected current in STN cell model. The repolarization phase of the AP is altered according to the ERG K+ ion channel activation time constant. The frequency of bursting discharge Again, the negative peak of the action potential hyperpolarization is more negative due to ERG K+ current.

Conclusion: The opening of ERG K+ channel reduced the resting membrane potential from ─65 mV to ─70 mV before generation of the action potential by the injected current in STN cell model. Thus, the ERG K+ channel openers may constitute a part of new pharmacological target towards treatment of the PD.

References: Gillies A, Willshaw D. Membrane channel interactions underlying rat subthalamic projection neuron rhythmic and bursting activity. Journal of neurophysiology. 2006 Apr 1;95(4):2352-65. Huang CS, Wang GH, Tai CH, Hu CC, Yang YC. Antiarrhythmics cure brain arrhythmia: The imperativeness of subthalamic ERG K+ channels in parkinsonian discharges. Science advances. 2017 May 1;3(5):e1602272.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/quantitative-study-of-subthalamic-erg-potassium-channels-in-parkinsonian-discharges/