Inhibition of high-voltage-activated calcium currents by acute hypoxia in cultured retinal ganglion cells

Hypoxia is a common factor of numerous ocular diseases that lead to dysfunctions and loss of retinal ganglion cells (RGCs) with subsequent vision loss. High-voltage-activated calcium channels are the main source of calcium entry into neurons. Their activity plays a central role in different signalin...

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Main Authors: Hanna Dumanska, Mariia Telka, Nikolai Veselovsky
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fncel.2023.1202083/full
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author Hanna Dumanska
Mariia Telka
Nikolai Veselovsky
author_facet Hanna Dumanska
Mariia Telka
Nikolai Veselovsky
author_sort Hanna Dumanska
collection DOAJ
description Hypoxia is a common factor of numerous ocular diseases that lead to dysfunctions and loss of retinal ganglion cells (RGCs) with subsequent vision loss. High-voltage-activated calcium channels are the main source of calcium entry into neurons. Their activity plays a central role in different signaling processes in health and diseases, such as enzyme activation, gene transcription, synaptic transmission, or the onset of cell death. This study aims to establish and evaluate the initial effect of the early stage of acute hypoxia on somatic HVA calcium currents in cultured RGCs. HVA calcium currents were recorded in RGCs using the whole-cell patch-clamp technique in the voltage-clamp mode. The fast local superfusion was used for a brief (up to 270 s) application of the hypoxic solution (pO2 < 5 mmHg). The switch from normoxic to hypoxic solutions and vice versa was less than 1 s. The HVA calcium channel activity was inhibited by acute hypoxia in 79% of RGCs (30 of 38 RGCs) in a strong voltage-dependent manner. The level of inhibition was independent of the duration of hypoxia or repeated applications. The hypoxia-induced inhibition of calcium currents had a strong correlation with the duration of hypoxia and showed the transition from reversible to irreversible at 75 s of hypoxia and longer. The results obtained are the first demonstration of the phenomena of HVA calcium current inhibition by acute hypoxia in RGCs and provide a conceptual framework for further research.
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spelling doaj.art-6e896b8898cb4b52b19ee8cc8d722df22023-07-03T07:24:40ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-07-011710.3389/fncel.2023.12020831202083Inhibition of high-voltage-activated calcium currents by acute hypoxia in cultured retinal ganglion cellsHanna DumanskaMariia TelkaNikolai VeselovskyHypoxia is a common factor of numerous ocular diseases that lead to dysfunctions and loss of retinal ganglion cells (RGCs) with subsequent vision loss. High-voltage-activated calcium channels are the main source of calcium entry into neurons. Their activity plays a central role in different signaling processes in health and diseases, such as enzyme activation, gene transcription, synaptic transmission, or the onset of cell death. This study aims to establish and evaluate the initial effect of the early stage of acute hypoxia on somatic HVA calcium currents in cultured RGCs. HVA calcium currents were recorded in RGCs using the whole-cell patch-clamp technique in the voltage-clamp mode. The fast local superfusion was used for a brief (up to 270 s) application of the hypoxic solution (pO2 < 5 mmHg). The switch from normoxic to hypoxic solutions and vice versa was less than 1 s. The HVA calcium channel activity was inhibited by acute hypoxia in 79% of RGCs (30 of 38 RGCs) in a strong voltage-dependent manner. The level of inhibition was independent of the duration of hypoxia or repeated applications. The hypoxia-induced inhibition of calcium currents had a strong correlation with the duration of hypoxia and showed the transition from reversible to irreversible at 75 s of hypoxia and longer. The results obtained are the first demonstration of the phenomena of HVA calcium current inhibition by acute hypoxia in RGCs and provide a conceptual framework for further research.https://www.frontiersin.org/articles/10.3389/fncel.2023.1202083/fullretinal ganglion cellssomatic calcium channelshigh-voltage-activated calcium currentsacute hypoxiareversible and irreversible inhibition
spellingShingle Hanna Dumanska
Mariia Telka
Nikolai Veselovsky
Inhibition of high-voltage-activated calcium currents by acute hypoxia in cultured retinal ganglion cells
Frontiers in Cellular Neuroscience
retinal ganglion cells
somatic calcium channels
high-voltage-activated calcium currents
acute hypoxia
reversible and irreversible inhibition
title Inhibition of high-voltage-activated calcium currents by acute hypoxia in cultured retinal ganglion cells
title_full Inhibition of high-voltage-activated calcium currents by acute hypoxia in cultured retinal ganglion cells
title_fullStr Inhibition of high-voltage-activated calcium currents by acute hypoxia in cultured retinal ganglion cells
title_full_unstemmed Inhibition of high-voltage-activated calcium currents by acute hypoxia in cultured retinal ganglion cells
title_short Inhibition of high-voltage-activated calcium currents by acute hypoxia in cultured retinal ganglion cells
title_sort inhibition of high voltage activated calcium currents by acute hypoxia in cultured retinal ganglion cells
topic retinal ganglion cells
somatic calcium channels
high-voltage-activated calcium currents
acute hypoxia
reversible and irreversible inhibition
url https://www.frontiersin.org/articles/10.3389/fncel.2023.1202083/full
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AT mariiatelka inhibitionofhighvoltageactivatedcalciumcurrentsbyacutehypoxiainculturedretinalganglioncells
AT nikolaiveselovsky inhibitionofhighvoltageactivatedcalciumcurrentsbyacutehypoxiainculturedretinalganglioncells