Cargando…
The reverse mode of the Na(+)/Ca(2+) exchanger contributes to the pacemaker mechanism in rabbit sinus node cells
Sinus node (SN) pacemaking is based on a coupling between surface membrane ion-channels and intracellular Ca(2+)-handling. The fundamental role of the inward Na(+)/Ca(2+) exchanger (NCX) is firmly established. However, little is known about the reverse mode exchange. A simulation study attributed im...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9759562/ https://www.ncbi.nlm.nih.gov/pubmed/36528651 http://dx.doi.org/10.1038/s41598-022-25574-8 |
_version_ | 1784852260526751744 |
---|---|
author | Tóth, Noémi Loewe, Axel Szlovák, Jozefina Kohajda, Zsófia Bitay, Gergő Levijoki, Jouko Papp, Julius Gy. Varró, András Nagy, Norbert |
author_facet | Tóth, Noémi Loewe, Axel Szlovák, Jozefina Kohajda, Zsófia Bitay, Gergő Levijoki, Jouko Papp, Julius Gy. Varró, András Nagy, Norbert |
author_sort | Tóth, Noémi |
collection | PubMed |
description | Sinus node (SN) pacemaking is based on a coupling between surface membrane ion-channels and intracellular Ca(2+)-handling. The fundamental role of the inward Na(+)/Ca(2+) exchanger (NCX) is firmly established. However, little is known about the reverse mode exchange. A simulation study attributed important role to reverse NCX activity, however experimental evidence is still missing. Whole-cell and perforated patch-clamp experiments were performed on rabbit SN cells supplemented with fluorescent Ca(2+)-tracking. We established 2 and 8 mM pipette NaCl groups to suppress and enable reverse NCX. NCX was assessed by specific block with 1 μM ORM-10962. Mechanistic simulations were performed by Maltsev–Lakatta minimal computational SN model. Active reverse NCX resulted in larger Ca(2+)-transient amplitude with larger SR Ca(2+)-content. Spontaneous action potential (AP) frequency increased with 8 mM NaCl. When reverse NCX was facilitated by 1 μM strophantin the Ca(2+)(i) and spontaneous rate increased. ORM-10962 applied prior to strophantin prevented Ca(2+)(i) and AP cycle change. Computational simulations indicated gradually increasing reverse NCX current, Ca(2+)(i) and heart rate with increasing Na(+)(i). Our results provide further evidence for the role of reverse NCX in SN pacemaking. The reverse NCX activity may provide additional Ca(2+)-influx that could increase SR Ca(2+)-content, which consequently leads to enhanced pacemaking activity. |
format | Online Article Text |
id | pubmed-9759562 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-97595622022-12-19 The reverse mode of the Na(+)/Ca(2+) exchanger contributes to the pacemaker mechanism in rabbit sinus node cells Tóth, Noémi Loewe, Axel Szlovák, Jozefina Kohajda, Zsófia Bitay, Gergő Levijoki, Jouko Papp, Julius Gy. Varró, András Nagy, Norbert Sci Rep Article Sinus node (SN) pacemaking is based on a coupling between surface membrane ion-channels and intracellular Ca(2+)-handling. The fundamental role of the inward Na(+)/Ca(2+) exchanger (NCX) is firmly established. However, little is known about the reverse mode exchange. A simulation study attributed important role to reverse NCX activity, however experimental evidence is still missing. Whole-cell and perforated patch-clamp experiments were performed on rabbit SN cells supplemented with fluorescent Ca(2+)-tracking. We established 2 and 8 mM pipette NaCl groups to suppress and enable reverse NCX. NCX was assessed by specific block with 1 μM ORM-10962. Mechanistic simulations were performed by Maltsev–Lakatta minimal computational SN model. Active reverse NCX resulted in larger Ca(2+)-transient amplitude with larger SR Ca(2+)-content. Spontaneous action potential (AP) frequency increased with 8 mM NaCl. When reverse NCX was facilitated by 1 μM strophantin the Ca(2+)(i) and spontaneous rate increased. ORM-10962 applied prior to strophantin prevented Ca(2+)(i) and AP cycle change. Computational simulations indicated gradually increasing reverse NCX current, Ca(2+)(i) and heart rate with increasing Na(+)(i). Our results provide further evidence for the role of reverse NCX in SN pacemaking. The reverse NCX activity may provide additional Ca(2+)-influx that could increase SR Ca(2+)-content, which consequently leads to enhanced pacemaking activity. Nature Publishing Group UK 2022-12-17 /pmc/articles/PMC9759562/ /pubmed/36528651 http://dx.doi.org/10.1038/s41598-022-25574-8 Text en © The Author(s) 2022 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/) . |
spellingShingle | Article Tóth, Noémi Loewe, Axel Szlovák, Jozefina Kohajda, Zsófia Bitay, Gergő Levijoki, Jouko Papp, Julius Gy. Varró, András Nagy, Norbert The reverse mode of the Na(+)/Ca(2+) exchanger contributes to the pacemaker mechanism in rabbit sinus node cells |
title | The reverse mode of the Na(+)/Ca(2+) exchanger contributes to the pacemaker mechanism in rabbit sinus node cells |
title_full | The reverse mode of the Na(+)/Ca(2+) exchanger contributes to the pacemaker mechanism in rabbit sinus node cells |
title_fullStr | The reverse mode of the Na(+)/Ca(2+) exchanger contributes to the pacemaker mechanism in rabbit sinus node cells |
title_full_unstemmed | The reverse mode of the Na(+)/Ca(2+) exchanger contributes to the pacemaker mechanism in rabbit sinus node cells |
title_short | The reverse mode of the Na(+)/Ca(2+) exchanger contributes to the pacemaker mechanism in rabbit sinus node cells |
title_sort | reverse mode of the na(+)/ca(2+) exchanger contributes to the pacemaker mechanism in rabbit sinus node cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9759562/ https://www.ncbi.nlm.nih.gov/pubmed/36528651 http://dx.doi.org/10.1038/s41598-022-25574-8 |
work_keys_str_mv | AT tothnoemi thereversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT loeweaxel thereversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT szlovakjozefina thereversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT kohajdazsofia thereversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT bitaygergo thereversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT levijokijouko thereversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT pappjuliusgy thereversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT varroandras thereversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT nagynorbert thereversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT tothnoemi reversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT loeweaxel reversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT szlovakjozefina reversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT kohajdazsofia reversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT bitaygergo reversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT levijokijouko reversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT pappjuliusgy reversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT varroandras reversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells AT nagynorbert reversemodeofthenaca2exchangercontributestothepacemakermechanisminrabbitsinusnodecells |