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Altered Na/Ca exchange distribution in ventricular myocytes from failing hearts
In mammalian cardiac ventricular myocytes, Ca efflux via Na/Ca exchange (NCX) occurs predominantly at T tubules. Heart failure is associated with disrupted t-tubular structure, but its effect on t-tubular function is less clear. We therefore investigated t-tubular NCX activity in ventricular myocyte...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Physiological Society
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4796630/ https://www.ncbi.nlm.nih.gov/pubmed/26566728 http://dx.doi.org/10.1152/ajpheart.00597.2015 |
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author | Gadeberg, Hanne C. Bryant, Simon M. James, Andrew F. Orchard, Clive H. |
author_facet | Gadeberg, Hanne C. Bryant, Simon M. James, Andrew F. Orchard, Clive H. |
author_sort | Gadeberg, Hanne C. |
collection | PubMed |
description | In mammalian cardiac ventricular myocytes, Ca efflux via Na/Ca exchange (NCX) occurs predominantly at T tubules. Heart failure is associated with disrupted t-tubular structure, but its effect on t-tubular function is less clear. We therefore investigated t-tubular NCX activity in ventricular myocytes isolated from rat hearts ∼18 wk after coronary artery ligation (CAL) or corresponding sham operation (Sham). NCX current (I(NCX)) and l-type Ca current (I(Ca)) were recorded using the whole cell, voltage-clamp technique in intact and detubulated (DT) myocytes; intracellular free Ca concentration ([Ca](i)) was monitored simultaneously using fluo-4. I(NCX) was activated and measured during application of caffeine to release Ca from sarcoplasmic reticulum (SR). Whole cell I(NCX) was not significantly different in Sham and CAL myocytes and occurred predominantly in the T tubules in Sham myocytes. CAL was associated with redistribution of I(NCX) and I(Ca) away from the T tubules to the cell surface and an increase in t-tubular I(NCX)/I(Ca) density from 0.12 in Sham to 0.30 in CAL myocytes. The decrease in t-tubular I(NCX) in CAL myocytes was accompanied by an increase in the fraction of Ca sequestered by SR. However, SR Ca content was not significantly different in Sham, Sham DT, and CAL myocytes but was significantly increased by DT of CAL myocytes. In Sham myocytes, there was hysteresis between I(NCX) and [Ca](i), which was absent in DT Sham but present in CAL and DT CAL myocytes. These data suggest altered distribution of NCX in CAL myocytes. |
format | Online Article Text |
id | pubmed-4796630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Physiological Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-47966302016-03-23 Altered Na/Ca exchange distribution in ventricular myocytes from failing hearts Gadeberg, Hanne C. Bryant, Simon M. James, Andrew F. Orchard, Clive H. Am J Physiol Heart Circ Physiol Cardiac Excitation and Contraction In mammalian cardiac ventricular myocytes, Ca efflux via Na/Ca exchange (NCX) occurs predominantly at T tubules. Heart failure is associated with disrupted t-tubular structure, but its effect on t-tubular function is less clear. We therefore investigated t-tubular NCX activity in ventricular myocytes isolated from rat hearts ∼18 wk after coronary artery ligation (CAL) or corresponding sham operation (Sham). NCX current (I(NCX)) and l-type Ca current (I(Ca)) were recorded using the whole cell, voltage-clamp technique in intact and detubulated (DT) myocytes; intracellular free Ca concentration ([Ca](i)) was monitored simultaneously using fluo-4. I(NCX) was activated and measured during application of caffeine to release Ca from sarcoplasmic reticulum (SR). Whole cell I(NCX) was not significantly different in Sham and CAL myocytes and occurred predominantly in the T tubules in Sham myocytes. CAL was associated with redistribution of I(NCX) and I(Ca) away from the T tubules to the cell surface and an increase in t-tubular I(NCX)/I(Ca) density from 0.12 in Sham to 0.30 in CAL myocytes. The decrease in t-tubular I(NCX) in CAL myocytes was accompanied by an increase in the fraction of Ca sequestered by SR. However, SR Ca content was not significantly different in Sham, Sham DT, and CAL myocytes but was significantly increased by DT of CAL myocytes. In Sham myocytes, there was hysteresis between I(NCX) and [Ca](i), which was absent in DT Sham but present in CAL and DT CAL myocytes. These data suggest altered distribution of NCX in CAL myocytes. American Physiological Society 2015-11-13 2016-01-15 /pmc/articles/PMC4796630/ /pubmed/26566728 http://dx.doi.org/10.1152/ajpheart.00597.2015 Text en Copyright © 2016 the American Physiological Society Licensed under Creative Commons Attribution CC-BY 3.0 (http://creativecommons.org/licenses/by/3.0/deed.en_US) : © the American Physiological Society. |
spellingShingle | Cardiac Excitation and Contraction Gadeberg, Hanne C. Bryant, Simon M. James, Andrew F. Orchard, Clive H. Altered Na/Ca exchange distribution in ventricular myocytes from failing hearts |
title | Altered Na/Ca exchange distribution in ventricular myocytes from failing hearts |
title_full | Altered Na/Ca exchange distribution in ventricular myocytes from failing hearts |
title_fullStr | Altered Na/Ca exchange distribution in ventricular myocytes from failing hearts |
title_full_unstemmed | Altered Na/Ca exchange distribution in ventricular myocytes from failing hearts |
title_short | Altered Na/Ca exchange distribution in ventricular myocytes from failing hearts |
title_sort | altered na/ca exchange distribution in ventricular myocytes from failing hearts |
topic | Cardiac Excitation and Contraction |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4796630/ https://www.ncbi.nlm.nih.gov/pubmed/26566728 http://dx.doi.org/10.1152/ajpheart.00597.2015 |
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