AUTHOR=Alshawaf Abdullah J. , Alnassar Sarah A. , Al-Mohanna Futwan A. TITLE=The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitro JOURNAL=Frontiers in Cellular Neuroscience VOLUME=17 YEAR=2023 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2023.1118335 DOI=10.3389/fncel.2023.1118335 ISSN=1662-5102 ABSTRACT=

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.