Drosophila Voltage-Gated Calcium Channel α1-Subunits Regulate Cardiac Function in the Aging Heart

Abstract Ion channels maintain numerous physiological functions and regulate signaling pathways. They are the key targets for cellular reactive oxygen species (ROS), acting as signaling switches between ROS and ionic homeostasis. We have carried out a paraquat (PQ) screen in Drosophila to identify i...

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Autores principales: Alexander Lam, Priyanka Karekar, Kajol Shah, Girija Hariharan, Michelle Fleyshman, Harmehak Kaur, Harpreet Singh, Shubha Gururaja Rao
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Lenguaje:EN
Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/499678ac994a4f2d93c894804e6d6863
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spelling oai:doaj.org-article:499678ac994a4f2d93c894804e6d68632021-12-02T16:08:27ZDrosophila Voltage-Gated Calcium Channel α1-Subunits Regulate Cardiac Function in the Aging Heart10.1038/s41598-018-25195-02045-2322https://doaj.org/article/499678ac994a4f2d93c894804e6d68632018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25195-0https://doaj.org/toc/2045-2322Abstract Ion channels maintain numerous physiological functions and regulate signaling pathways. They are the key targets for cellular reactive oxygen species (ROS), acting as signaling switches between ROS and ionic homeostasis. We have carried out a paraquat (PQ) screen in Drosophila to identify ion channels regulating the ROS handling and survival in Drosophila melanogaster. Our screen has revealed that α1-subunits (D-type, T-type, and cacophony) of voltage-gated calcium channels (VGCCs) handle PQ-mediated ROS stress differentially in a gender-based manner. Since ROS are also involved in determining the lifespan, we discovered that the absence of T-type and cacophony decreased the lifespan while the absence of D-type maintained a similar lifespan to that of the wild-type strain. VGCCs are also responsible for electrical signaling in cardiac cells. The cardiac function of each mutant was evaluated through optical coherence tomography (OCT), which revealed that α1-subunits of VGCCs are essential in maintaining cardiac rhythmicity and cardiac function in an age-dependent manner. Our results establish specific roles of α1-subunits of VGCCs in the functioning of the aging heart.Alexander LamPriyanka KarekarKajol ShahGirija HariharanMichelle FleyshmanHarmehak KaurHarpreet SinghShubha Gururaja RaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Alexander Lam
Priyanka Karekar
Kajol Shah
Girija Hariharan
Michelle Fleyshman
Harmehak Kaur
Harpreet Singh
Shubha Gururaja Rao
Drosophila Voltage-Gated Calcium Channel α1-Subunits Regulate Cardiac Function in the Aging Heart
description Abstract Ion channels maintain numerous physiological functions and regulate signaling pathways. They are the key targets for cellular reactive oxygen species (ROS), acting as signaling switches between ROS and ionic homeostasis. We have carried out a paraquat (PQ) screen in Drosophila to identify ion channels regulating the ROS handling and survival in Drosophila melanogaster. Our screen has revealed that α1-subunits (D-type, T-type, and cacophony) of voltage-gated calcium channels (VGCCs) handle PQ-mediated ROS stress differentially in a gender-based manner. Since ROS are also involved in determining the lifespan, we discovered that the absence of T-type and cacophony decreased the lifespan while the absence of D-type maintained a similar lifespan to that of the wild-type strain. VGCCs are also responsible for electrical signaling in cardiac cells. The cardiac function of each mutant was evaluated through optical coherence tomography (OCT), which revealed that α1-subunits of VGCCs are essential in maintaining cardiac rhythmicity and cardiac function in an age-dependent manner. Our results establish specific roles of α1-subunits of VGCCs in the functioning of the aging heart.
format article
author Alexander Lam
Priyanka Karekar
Kajol Shah
Girija Hariharan
Michelle Fleyshman
Harmehak Kaur
Harpreet Singh
Shubha Gururaja Rao
author_facet Alexander Lam
Priyanka Karekar
Kajol Shah
Girija Hariharan
Michelle Fleyshman
Harmehak Kaur
Harpreet Singh
Shubha Gururaja Rao
author_sort Alexander Lam
title Drosophila Voltage-Gated Calcium Channel α1-Subunits Regulate Cardiac Function in the Aging Heart
title_short Drosophila Voltage-Gated Calcium Channel α1-Subunits Regulate Cardiac Function in the Aging Heart
title_full Drosophila Voltage-Gated Calcium Channel α1-Subunits Regulate Cardiac Function in the Aging Heart
title_fullStr Drosophila Voltage-Gated Calcium Channel α1-Subunits Regulate Cardiac Function in the Aging Heart
title_full_unstemmed Drosophila Voltage-Gated Calcium Channel α1-Subunits Regulate Cardiac Function in the Aging Heart
title_sort drosophila voltage-gated calcium channel α1-subunits regulate cardiac function in the aging heart
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/499678ac994a4f2d93c894804e6d6863
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