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Conversations with a Neuron, Volume 4

Neurons are Not Made Equal: Potential Seizure Treatment for Children?

The study determined that not all neurons are created equal and that some neurons are more active compared to others.

Author: Tenzin Nordon

Neurophysiology

Introduction 

A sodium-potassium pump (Na+/K+ pump) is a type of protein pump that is found in the cell membrane of neurons (Pirahanchi et al., 2021). The sodium potassium pump helps maintain the different concentrations of ions inside and outside the cell, which is also known as a concentration gradient. The concentration gradient determines the membrane potential of a cell, which is the electrical potential between the inner and outer membrane of a cell (Chrysafides et al., 2019). It is known that there are four different sub-types of sodium-potassium pumps and certain properties of the Na+/K+ pumps play a role in seizures (Krishnan et al., 2015). However, the functions of Na+/K+ pumps have not been studied thoroughly in developing brains. In a paper recently published by the Journal of Neurophysiology, Shao et al., (2021) investigated the roles of a Na+/K+ pump in two different neurons in the hippocampus during brain development. The hippocampus is a region of the brain known to play a major role in memory and learning (Anand & Dhikav, 2012). The two neurons that were examined are called pyramidal neurons which are from CA1 and CA3 regions of the hippocampus (figure 1). The study found that Na+/K+ pumps have different levels of activation in different types of developing neurons. The different activation levels of the protein pumps cause varying excitability properties in neurons. The implications of these findings are significant as they could be potential indications for seizure treatments in children. 

 

 

Image shows neurons within hippocampus layers in brain cartoon
Figure 1. The layers of the hippocampus in a human brain (3 layers): CA1 pyramidal neurons and CA3 pyramidal neurons.
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Background

Epilepsy is a neurological disorder in which brain activity becomes abnormal; repetition of seizure being the main symptom (Guerrini, 2006). Seizures are bursts of uncontrollable electrical activ

ity in the brain which causes temporary changes in muscle movement, behavior, or state of awareness. Excitability is when a neuron responds to a stimulus by causing a rapid change in membrane potential. Depending on the property of a neuron, certain neurons can transition from a resting state to an excited state. Understanding the effects of Na+/K+ pump on neuronal excitability in a developing brain could be used to better understand how seizures generate in children, so a new treatment for epilepsy can be developed. Epilepsy affects over 70 million people worldwide, 10.5 millions of those being children (Thijs et al., 2019; Guerrini, 2006). There is no cure for epilepsy, but it can be managed with medications. The flaws of current seizure medications are long-term addictive potential and limitations of therapeutic effects. 

Methods

The main method of conducting the experiments was electrophysiology. Sprague-Dawley rats were anesthetized and decapitated 9 to 13 days postnatal. The rat brains were harvested, and hippocampal slices were prepared. About 1 to 2 hours after the hippocampal slices were placed in a submerged recording chamber. Extracellular field potential recordings and whole cell recordings were conducted on the CA3 and CA1 region of the hippocampal slices. The whole cell recording looked at the electrical properties of one cell, either CA1 or CA3. The field recording looked at the electrical property of a whole group of neurons in the CA1 and CA3 regions of the hippocampus. Bursts of electrical activity were induced, then the Na+/K+ pumps were blocked into a solution medium. This would allow for the neuron's electrical activity to be overserved. Then there was a qualitative data analysis.  

Results

The study by Shao et al., (2021) seemed to find a significant difference in Na+/K+ pump function in developing CA3 neurons vs CA1 neurons. The findings supported that the protein pump played a greater role in the CA3 neuron than CA1 neurons. The Na+/K+ pumps are more active in CA3 neurons, which indicated that the protein pumps have more impact on their neuronal excitability than CA1 neurons. Bursts of electrical activity that fire at the same time in developing CA3 neurons ceased when the protein pump was blocked and the developing CA3 neurons. 

Discussion

The primary purpose of this study was to determine the functions of the Na+/K+ pump in different neurons when the brain is still developing. Overall, the study found that all neurons are not built the same and have very different properties. The two neurons that were compared had different excitability properties when looking at the functions of Na+/K+ pumps. When the Na+/K+ pump blocker was added during the CA3 neurons bursts of action potential, there was an ending of the bursts of activity. This indicated the Na+/K+ pump could be a mechanism for controlling seizures in developing brains. The blockage of Na+/K+ pumps have been used to treat heart failure for a long time (Shao et al., 2021). Although there were no direct implications of Na+/K+ pumps being a therapeutic treatment this study gives a good base for future studies that could be conducted to see the possibility of treatment options. 


 

[+] References

1.

Anand, K. S., & Dhikav, V. (2012). Hippocampus in health and disease: An overview. Annals of Indian Academy of Neurology15(4), 239.

 

2.

Chrysafides, S. M., Bordes, S., & Sharma, S. (2019). Physiology, Resting Potential.

3.

Guerrini, R. (2006). Epilepsy in children. The Lancet367(9509), 499-524.

 

4.

Krishnan, G. P., Filatov, G., Shilnikov, A., & Bazhenov, M. (2015). Electrogenic properties of the Na+/K+ ATPase control transitions between normal and pathological brain states. Journal of neurophysiology113(9), 3356-3374.

5.

Pirahanchi, Y., Jessu, R., & Aeddula, N. R. (2021). Physiology, sodium potassium pump. In StatPearls [Internet]. StatPearls Publishing.

 

6.

Shao, L. R., Janicot, R., & Stafstrom, C. E. (2021). Na+-K+-ATPase functions in the developing hippocampus: Regional differences in CA1 and CA3 neuronal excitability and role in epileptiform network bursting. Journal of neurophysiology, 125(1), 1-11. 

 

7.

Thijs, R. D., Surges, R., O'Brien, T. J., & Sander, J. W. (2019). Epilepsy in adults. The Lancet393(10172), 689-701.

 

 

[+] Other Work By Tenzin Nordon

The Two Subtypes of Parkinson’s Disease

Neuroanatomy

This article shows that Parkinson’s disease has two subtypes; brain-first and body-first. The body-first subtype seems to have a highly predictive marker of premotor RBD.