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Identification of RNA reads encoding different channels in isolated rat ventricular myocytes and the effect of cell stretching on L-type Ca(2+)current

BACKGROUND: The study aimed to identify transcripts of specific ion channels in rat ventricular cardiomyocytes and determine their potential role in the regulation of ionic currents in response to mechanical stimulation. The gene expression levels of various ion channels in freshly isolated rat vent...

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Autores principales: Kamkin, Andre G., Kamkina, Olga V., Kazansky, Viktor E., Mitrokhin, Vadim M., Bilichenko, Andrey, Nasedkina, Elizaveta A., Shileiko, Stanislav A., Rodina, Anastasia S., Zolotareva, Alexandra D., Zolotarev, Valentin I., Sutyagin, Pavel V., Mladenov, Mitko I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614344/
https://www.ncbi.nlm.nih.gov/pubmed/37899484
http://dx.doi.org/10.1186/s13062-023-00427-0
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author Kamkin, Andre G.
Kamkina, Olga V.
Kazansky, Viktor E.
Mitrokhin, Vadim M.
Bilichenko, Andrey
Nasedkina, Elizaveta A.
Shileiko, Stanislav A.
Rodina, Anastasia S.
Zolotareva, Alexandra D.
Zolotarev, Valentin I.
Sutyagin, Pavel V.
Mladenov, Mitko I.
author_facet Kamkin, Andre G.
Kamkina, Olga V.
Kazansky, Viktor E.
Mitrokhin, Vadim M.
Bilichenko, Andrey
Nasedkina, Elizaveta A.
Shileiko, Stanislav A.
Rodina, Anastasia S.
Zolotareva, Alexandra D.
Zolotarev, Valentin I.
Sutyagin, Pavel V.
Mladenov, Mitko I.
author_sort Kamkin, Andre G.
collection PubMed
description BACKGROUND: The study aimed to identify transcripts of specific ion channels in rat ventricular cardiomyocytes and determine their potential role in the regulation of ionic currents in response to mechanical stimulation. The gene expression levels of various ion channels in freshly isolated rat ventricular cardiomyocytes were investigated using the RNA-seq technique. We also measured changes in current through Ca(V)1.2 channels under cell stretching using the whole-cell patch-clamp method. RESULTS: Among channels that showed mechanosensitivity, significant amounts of TRPM7, TRPC1, and TRPM4 transcripts were found. We suppose that the recorded L-type Ca(2+) current is probably expressed through Ca(V)1.2. Furthermore, stretching cells by 6, 8, and 10 μm, which increases I(SAC) through the TRPM7, TRPC1, and TRPM4 channels, also decreased I(Ca,L) through the Ca(V)1.2 channels in K(+) (in)/K(+) (out), Cs(+) (in)/K(+) (out), K(+) (in)/Cs(+) (out), and Cs(+) (in)/Cs(+) (out) solutions. The application of a nonspecific I(SAC) blocker, Gd(3+), during cell stretching eliminated I(SAC) through nonselective cation channels and I(Ca,L) through Ca(V)1.2 channels. Since the response to Gd(3+) was maintained in Cs(+) (in)/Cs(+) (out) solutions, we suggest that voltage-gated Ca(V)1.2 channels in the ventricular myocytes of adult rats also exhibit mechanosensitive properties. CONCLUSIONS: Our findings suggest that TRPM7, TRPC1, and TRPM4 channels represent stretch-activated nonselective cation channels in rat ventricular myocytes. Probably the Ca(V)1.2 channels in these cells exhibit mechanosensitive properties. Our results provide insight into the molecular mechanisms underlying stretch-induced responses in rat ventricular myocytes, which may have implications for understanding cardiac physiology and pathophysiology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00427-0.
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spelling pubmed-106143442023-10-31 Identification of RNA reads encoding different channels in isolated rat ventricular myocytes and the effect of cell stretching on L-type Ca(2+)current Kamkin, Andre G. Kamkina, Olga V. Kazansky, Viktor E. Mitrokhin, Vadim M. Bilichenko, Andrey Nasedkina, Elizaveta A. Shileiko, Stanislav A. Rodina, Anastasia S. Zolotareva, Alexandra D. Zolotarev, Valentin I. Sutyagin, Pavel V. Mladenov, Mitko I. Biol Direct Research BACKGROUND: The study aimed to identify transcripts of specific ion channels in rat ventricular cardiomyocytes and determine their potential role in the regulation of ionic currents in response to mechanical stimulation. The gene expression levels of various ion channels in freshly isolated rat ventricular cardiomyocytes were investigated using the RNA-seq technique. We also measured changes in current through Ca(V)1.2 channels under cell stretching using the whole-cell patch-clamp method. RESULTS: Among channels that showed mechanosensitivity, significant amounts of TRPM7, TRPC1, and TRPM4 transcripts were found. We suppose that the recorded L-type Ca(2+) current is probably expressed through Ca(V)1.2. Furthermore, stretching cells by 6, 8, and 10 μm, which increases I(SAC) through the TRPM7, TRPC1, and TRPM4 channels, also decreased I(Ca,L) through the Ca(V)1.2 channels in K(+) (in)/K(+) (out), Cs(+) (in)/K(+) (out), K(+) (in)/Cs(+) (out), and Cs(+) (in)/Cs(+) (out) solutions. The application of a nonspecific I(SAC) blocker, Gd(3+), during cell stretching eliminated I(SAC) through nonselective cation channels and I(Ca,L) through Ca(V)1.2 channels. Since the response to Gd(3+) was maintained in Cs(+) (in)/Cs(+) (out) solutions, we suggest that voltage-gated Ca(V)1.2 channels in the ventricular myocytes of adult rats also exhibit mechanosensitive properties. CONCLUSIONS: Our findings suggest that TRPM7, TRPC1, and TRPM4 channels represent stretch-activated nonselective cation channels in rat ventricular myocytes. Probably the Ca(V)1.2 channels in these cells exhibit mechanosensitive properties. Our results provide insight into the molecular mechanisms underlying stretch-induced responses in rat ventricular myocytes, which may have implications for understanding cardiac physiology and pathophysiology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00427-0. BioMed Central 2023-10-30 /pmc/articles/PMC10614344/ /pubmed/37899484 http://dx.doi.org/10.1186/s13062-023-00427-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Kamkin, Andre G.
Kamkina, Olga V.
Kazansky, Viktor E.
Mitrokhin, Vadim M.
Bilichenko, Andrey
Nasedkina, Elizaveta A.
Shileiko, Stanislav A.
Rodina, Anastasia S.
Zolotareva, Alexandra D.
Zolotarev, Valentin I.
Sutyagin, Pavel V.
Mladenov, Mitko I.
Identification of RNA reads encoding different channels in isolated rat ventricular myocytes and the effect of cell stretching on L-type Ca(2+)current
title Identification of RNA reads encoding different channels in isolated rat ventricular myocytes and the effect of cell stretching on L-type Ca(2+)current
title_full Identification of RNA reads encoding different channels in isolated rat ventricular myocytes and the effect of cell stretching on L-type Ca(2+)current
title_fullStr Identification of RNA reads encoding different channels in isolated rat ventricular myocytes and the effect of cell stretching on L-type Ca(2+)current
title_full_unstemmed Identification of RNA reads encoding different channels in isolated rat ventricular myocytes and the effect of cell stretching on L-type Ca(2+)current
title_short Identification of RNA reads encoding different channels in isolated rat ventricular myocytes and the effect of cell stretching on L-type Ca(2+)current
title_sort identification of rna reads encoding different channels in isolated rat ventricular myocytes and the effect of cell stretching on l-type ca(2+)current
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614344/
https://www.ncbi.nlm.nih.gov/pubmed/37899484
http://dx.doi.org/10.1186/s13062-023-00427-0
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