» Articles » PMID: 33256465

Merits and Limitations of Studying Neuronal Depolarization-Dependent Processes Using Elevated External Potassium

Overview
Journal ASN Neuro
Specialties Chemistry
Neurology
Date 2020 Dec 1
PMID 33256465
Citations 31
Authors
Affiliations
Soon will be listed here.
Abstract

Elevated extracellular potassium chloride is widely used to achieve membrane depolarization of cultured neurons. This technique has illuminated mechanisms of calcium influx through L-type voltage sensitive calcium channels, activity-regulated signaling, downstream transcriptional events, and many other intracellular responses to depolarization. However, there is enormous variability in these treatments, including durations from seconds to days and concentrations from 3mM to 150 mM KCl. Differential effects of these variable protocols on neuronal activity and transcriptional programs are underexplored. Furthermore, potassium chloride treatments are criticized for being poor representatives of phenomena and are questioned for their effects on cell viability. In this review, we discuss the intracellular consequences of elevated extracellular potassium chloride treatment , the variability of such treatments in the literature, the strengths and limitations of this tool, and relevance of these studies to brain functions and dysfunctions.

Citing Articles

Neuronal Activity-Dependent Gene Dysregulation in iNeuronal Models of ALS/FTD Pathogenesis.

Ghaffari L, Welebob E, Boehringer A, Cyliax K, Pasinelli P, Trotti D bioRxiv. 2025; .

PMID: 39975241 PMC: 11838197. DOI: 10.1101/2025.01.27.632228.


Depolarization induces calcium-dependent BMP4 release from mouse embryonic palate mesenchymal cells.

Follmer M, Isner T, Ozekin Y, Levitt C, Burek C, Benninger R Nat Commun. 2024; 15(1):9806.

PMID: 39532850 PMC: 11558011. DOI: 10.1038/s41467-024-53642-2.


n-Butylidenephthalide recovered calcium homeostasis to ameliorate neurodegeneration of motor neurons derived from amyotrophic lateral sclerosis iPSCs.

Deng Y, Liu J, Ting H, Kuo T, Chiang C, Lin E PLoS One. 2024; 19(11):e0311573.

PMID: 39509425 PMC: 11542850. DOI: 10.1371/journal.pone.0311573.


Unveiling the cell biology of hippocampal neurons with dendritic axon origin.

Han Y, Hacker D, Donders B, Parperis C, Thuenauer R, Leterrier C J Cell Biol. 2024; 224(1).

PMID: 39495320 PMC: 11536041. DOI: 10.1083/jcb.202403141.


The e-Flower: A hydrogel-actuated 3D MEA for brain spheroid electrophysiology.

Martinelli E, Akouissi O, Liebi L, Furfaro I, Maula D, Savoia N Sci Adv. 2024; 10(42):eadp8054.

PMID: 39413178 PMC: 11482305. DOI: 10.1126/sciadv.adp8054.


References
1.
Morgan J, Cohen D, Hempstead J, Curran T . Mapping patterns of c-fos expression in the central nervous system after seizure. Science. 1987; 237(4811):192-7. DOI: 10.1126/science.3037702. View

2.
Kraig R, Nicholson C . Extracellular ionic variations during spreading depression. Neuroscience. 1978; 3(11):1045-59. DOI: 10.1016/0306-4522(78)90122-7. View

3.
Kovacs K, Steullet P, Steinmann M, Do K, Magistretti P, Halfon O . TORC1 is a calcium- and cAMP-sensitive coincidence detector involved in hippocampal long-term synaptic plasticity. Proc Natl Acad Sci U S A. 2007; 104(11):4700-5. PMC: 1838663. DOI: 10.1073/pnas.0607524104. View

4.
Bok J, Wang Q, Huang J, Green S . CaMKII and CaMKIV mediate distinct prosurvival signaling pathways in response to depolarization in neurons. Mol Cell Neurosci. 2007; 36(1):13-26. PMC: 2040167. DOI: 10.1016/j.mcn.2007.05.008. View

5.
Fujimura M, Usuki F . Methylmercury induces oxidative stress and subsequent neural hyperactivity leading to cell death through the p38 MAPK-CREB pathway in differentiated SH-SY5Y cells. Neurotoxicology. 2018; 67:226-233. DOI: 10.1016/j.neuro.2018.06.008. View