Objective: This study describe a quantitative investigation to explore the modulating effects of the ATP-dependent Potassium channel (KATP) ion channel conductance on spike patterns 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 and efficient treatment method. The firing properties of STN neurons in terms of single-spike or the burst modes modulate pathophysiological conditions in PD. Ion channel play dominant role in regulating firing properties of STN neurons.

Methods: Here the interpretation of KATP ion channel is based on conventional Hodgkin-Huxley formalism. Then the KATP 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 (Istim) to trigger action potential (AP) in the whole cell model. Then ATP internal concentration is varied to investigate the modulated response in AP and resting membrane potential.

Results: Voltage clamp protocol is used to generate KATP 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 KATP current in two ways. First, we increased the KATP channel maximum conductance by 50% of its control value to get the promising effects in action potential. Then, we reduced the ATPi (intracellular free ATP concentration) to 0.0001mM to get the same effects in action potential. The opening of KATP channel reduced the resting membrane potential from ─65mV to ─69mV before generation of the AP by the injected current in STN cell model. The rising phase of the AP is shifted towards right due to this hyperpolarization. Again, the negative peak of the action potential hyperpolarization is more negative due to KATP current.

Conclusions: The opening of KATP channel reduced the resting membrane potential from ─65mV to ─69mV before generation of the action potential by the injected current in STN cell model. As the KATP channel openers hyperpolarize the STN cell membrane by increasing K+ 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.

References: Shen KZ, Johnson SW. Ca2+ Influx through NMDA-gated channels activates ATP-sensitive K+ currents through a nitric oxide–cGMP pathway in subthalamic neurons. Journal of Neuroscience. 2010 Feb 3;30(5):1882-93. 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.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/contribution-of-atp-sensitive-potassium-channels-in-the-subthalamic-nucleus-neurons-towards-parkinsons-disease/