The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitro

Recent pharmacological studies demonstrate a role for zinc (Zn2+) in shaping intracellular calcium (Ca2+) dynamics and vice versa in excitable cells including neurons and cardiomyocytes. Herein, we sought to examine the dynamic of intracellular release of Ca2+ and Zn2+ upon modifying excitability of...

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Main Authors: Abdullah J. Alshawaf, Sarah A. Alnassar, Futwan A. Al-Mohanna
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fncel.2023.1118335/full
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author Abdullah J. Alshawaf
Abdullah J. Alshawaf
Sarah A. Alnassar
Futwan A. Al-Mohanna
author_facet Abdullah J. Alshawaf
Abdullah J. Alshawaf
Sarah A. Alnassar
Futwan A. Al-Mohanna
author_sort Abdullah J. Alshawaf
collection DOAJ
description Recent pharmacological studies demonstrate a role for zinc (Zn2+) in shaping intracellular calcium (Ca2+) dynamics and vice versa in excitable cells including neurons and cardiomyocytes. Herein, we sought to examine the dynamic of intracellular release of Ca2+ and Zn2+ upon modifying excitability of primary rat cortical neurons using electric field stimulation (EFS) in vitro. We show that exposure to EFS with an intensity of 7.69 V/cm induces transient membrane hyperpolarization together with transient elevations in the cytosolic levels of Ca2+ and Zn2+ ions. The EFS-induced hyperpolarization was inhibited by prior treatment of cells with the K+ channel opener diazoxide. Chemical hyperpolarization had no apparent effect on either Ca2+ or Zn2+. The source of EFS-induced rise in Ca2+ and Zn2+ seemed to be intracellular, and that the dynamic inferred of an interplay between Ca2+ and Zn2+ ions, whereby the removal of extracellular Ca2+ augmented the release of intracellular Ca2+ and Zn2+ and caused a stronger and more sustained hyperpolarization. We demonstrate that Zn2+ is released from intracellular vesicles located in the soma, with major co-localizations in the lysosomes and endoplasmic reticulum. These studies further support the use of EFS as a tool to interrogate the kinetics of intracellular ions in response to changing membrane potential in vitro.
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spelling doaj.art-60699c021fb743d48bc75ed99b788a6c2023-04-27T04:30:26ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-04-011710.3389/fncel.2023.11183351118335The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitroAbdullah J. Alshawaf0Abdullah J. Alshawaf1Sarah A. Alnassar2Futwan A. Al-Mohanna3Department of Physiological Sciences, College of Medicine, Alfaisal University, Riyadh, Saudi ArabiaDepartment of Cell Biology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of Cell Biology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of Cell Biology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaRecent pharmacological studies demonstrate a role for zinc (Zn2+) in shaping intracellular calcium (Ca2+) dynamics and vice versa in excitable cells including neurons and cardiomyocytes. Herein, we sought to examine the dynamic of intracellular release of Ca2+ and Zn2+ upon modifying excitability of primary rat cortical neurons using electric field stimulation (EFS) in vitro. We show that exposure to EFS with an intensity of 7.69 V/cm induces transient membrane hyperpolarization together with transient elevations in the cytosolic levels of Ca2+ and Zn2+ ions. The EFS-induced hyperpolarization was inhibited by prior treatment of cells with the K+ channel opener diazoxide. Chemical hyperpolarization had no apparent effect on either Ca2+ or Zn2+. The source of EFS-induced rise in Ca2+ and Zn2+ seemed to be intracellular, and that the dynamic inferred of an interplay between Ca2+ and Zn2+ ions, whereby the removal of extracellular Ca2+ augmented the release of intracellular Ca2+ and Zn2+ and caused a stronger and more sustained hyperpolarization. We demonstrate that Zn2+ is released from intracellular vesicles located in the soma, with major co-localizations in the lysosomes and endoplasmic reticulum. These studies further support the use of EFS as a tool to interrogate the kinetics of intracellular ions in response to changing membrane potential in vitro.https://www.frontiersin.org/articles/10.3389/fncel.2023.1118335/fullelectric field stimulationcalciumzincmembrane potentialcortical neurons
spellingShingle Abdullah J. Alshawaf
Abdullah J. Alshawaf
Sarah A. Alnassar
Futwan A. Al-Mohanna
The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitro
Frontiers in Cellular Neuroscience
electric field stimulation
calcium
zinc
membrane potential
cortical neurons
title The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitro
title_full The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitro
title_fullStr The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitro
title_full_unstemmed The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitro
title_short The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitro
title_sort interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitro
topic electric field stimulation
calcium
zinc
membrane potential
cortical neurons
url https://www.frontiersin.org/articles/10.3389/fncel.2023.1118335/full
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