Objective: Parkinson’s Disease (PD) is strongly linked to atypical electrical firing patterns in the neuronal cells of the globus pallidus externus (GPe), hence highlighting the significance of ion channel dysfunction in GPe cells as a pivotal factor in the pathogenesis of PD. This study aims to identify novel pharmacological targets for PD by investigating the impact of Nifedipine on the biophysical characteristics of ion channels in GPe cells.
Background: Efforts are underway to investigate novel pharmacological targets to reduce dependence on high-dose levodopa treatment for PD.
Method: A computer-based model was built to replicate the electrical activity of individual GPe cells. This conceptual framework encompasses the entirety of the functional ion channels, pumps, and exchangers present inside the cellular membrane. We utilized a multi-dose model of Nifedipine (1, 5, and 10 μmol) to induce changes in the maximum conductance of voltage-gated L-type Ca2+ channels.
Results: The membrane potential was measured using the current clamp methods, with a stimulus of 1 nA and a duration of 1 ms. When exposed to a current stimulation of 1 nA, the GPe cell model displayed a resting membrane potential (RMP) of -50 mV and generated action potentials (AP) in single-spike mode. The administration of 1 and 5 μmol of Nifedipine resulted in a decrease in the amplitude of the AP to 9 mV and 4 mV, respectively. The administration of a 10 μmol dose of Nifedipine led to a decrease in the RMP to -63 mV, thereby halting the formation of APs and diminishing the excitability of the cell.
Conclusion: This study highlights the role of L-type calcium channel currents in the generation of burst discharges in GPe neurons under the influence of Nifedipine. The presented data provide evidence in favour of employing a precise dose of Nifedipine as a feasible pharmaceutical intervention for PD, excluding the involvement of dopamine.
To cite this abstract in AMA style:
G. Kuanar, C. Mahapatra. A Quantitative Investigation has Revealed Nifedipine as a Possible Pharmacological Modulator in Parkinson’s Disease [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/a-quantitative-investigation-has-revealed-nifedipine-as-a-possible-pharmacological-modulator-in-parkinsons-disease/. Accessed June 15, 2025.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-quantitative-investigation-has-revealed-nifedipine-as-a-possible-pharmacological-modulator-in-parkinsons-disease/