Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells
Uptake and release calcium from the sarcoplasmic reticulum (SR) (dubbed “calcium clock”), in the form of spontaneous, rhythmic, local diastolic calcium releases (LCRs), together with voltage-sensitive ion channels (membrane clock) form a coupled system that regulates the action potential (AP) firing...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612473/ https://www.ncbi.nlm.nih.gov/pubmed/28945810 http://dx.doi.org/10.1371/journal.pone.0185222 |
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author | Sirenko, Syevda G. Yang, Dongmei Maltseva, Larissa A. Kim, Mary S. Lakatta, Edward G. Maltsev, Victor A. |
author_facet | Sirenko, Syevda G. Yang, Dongmei Maltseva, Larissa A. Kim, Mary S. Lakatta, Edward G. Maltsev, Victor A. |
author_sort | Sirenko, Syevda G. |
collection | PubMed |
description | Uptake and release calcium from the sarcoplasmic reticulum (SR) (dubbed “calcium clock”), in the form of spontaneous, rhythmic, local diastolic calcium releases (LCRs), together with voltage-sensitive ion channels (membrane clock) form a coupled system that regulates the action potential (AP) firing rate. LCRs activate Sodium/Calcium exchanger (NCX) that accelerates diastolic depolarization and thus participating in regulation of the time at which the next AP will occur. Previous studies in rabbit SA node cells (SANC) demonstrated that the basal AP cycle length (APCL) is tightly coupled to the basal LCR period (time from the prior AP-induced Ca(2+) transient to the diastolic LCR occurrence), and that this coupling is further modulated by autonomic receptor stimulation. Although spontaneous LCRs during diastolic depolarization have been reported in SANC of various species (rabbit, cat, mouse, toad), prior studies have failed to detect LCRs in spontaneously beating SANC of guinea-pig, a species that has been traditionally used in studies of cardiac pacemaker cell function. We performed a detailed investigation of whether guinea-pig SANC generate LCRs and whether they play a similar key role in regulation of the AP firing rate. We used two different approaches, 2D high-speed camera and classical line-scan confocal imaging. Positioning the scan-line beneath sarcolemma, parallel to the long axis of the cell, we found that rhythmically beating guinea-pig SANC do, indeed, generate spontaneous, diastolic LCRs beneath the surface membrane. The average key LCR characteristics measured in confocal images in guinea-pig SANC were comparable to rabbit SANC, both in the basal state and in the presence of β-adrenergic receptor stimulation. Moreover, the relationship between the LCR period and APCL was subtended by the same linear function. Thus, LCRs in guinea-pig SANC contribute to the diastolic depolarization and APCL regulation. Our findings indicate that coupled-clock system regulation of APCL is a general, species-independent, mechanism of pacemaker cell normal automaticity. Lack of LCRs in prior studies is likely explained by technical issues, as individual LCRs are small stochastic events occurring mainly near the cell border. |
format | Online Article Text |
id | pubmed-5612473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-56124732017-10-09 Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells Sirenko, Syevda G. Yang, Dongmei Maltseva, Larissa A. Kim, Mary S. Lakatta, Edward G. Maltsev, Victor A. PLoS One Research Article Uptake and release calcium from the sarcoplasmic reticulum (SR) (dubbed “calcium clock”), in the form of spontaneous, rhythmic, local diastolic calcium releases (LCRs), together with voltage-sensitive ion channels (membrane clock) form a coupled system that regulates the action potential (AP) firing rate. LCRs activate Sodium/Calcium exchanger (NCX) that accelerates diastolic depolarization and thus participating in regulation of the time at which the next AP will occur. Previous studies in rabbit SA node cells (SANC) demonstrated that the basal AP cycle length (APCL) is tightly coupled to the basal LCR period (time from the prior AP-induced Ca(2+) transient to the diastolic LCR occurrence), and that this coupling is further modulated by autonomic receptor stimulation. Although spontaneous LCRs during diastolic depolarization have been reported in SANC of various species (rabbit, cat, mouse, toad), prior studies have failed to detect LCRs in spontaneously beating SANC of guinea-pig, a species that has been traditionally used in studies of cardiac pacemaker cell function. We performed a detailed investigation of whether guinea-pig SANC generate LCRs and whether they play a similar key role in regulation of the AP firing rate. We used two different approaches, 2D high-speed camera and classical line-scan confocal imaging. Positioning the scan-line beneath sarcolemma, parallel to the long axis of the cell, we found that rhythmically beating guinea-pig SANC do, indeed, generate spontaneous, diastolic LCRs beneath the surface membrane. The average key LCR characteristics measured in confocal images in guinea-pig SANC were comparable to rabbit SANC, both in the basal state and in the presence of β-adrenergic receptor stimulation. Moreover, the relationship between the LCR period and APCL was subtended by the same linear function. Thus, LCRs in guinea-pig SANC contribute to the diastolic depolarization and APCL regulation. Our findings indicate that coupled-clock system regulation of APCL is a general, species-independent, mechanism of pacemaker cell normal automaticity. Lack of LCRs in prior studies is likely explained by technical issues, as individual LCRs are small stochastic events occurring mainly near the cell border. Public Library of Science 2017-09-25 /pmc/articles/PMC5612473/ /pubmed/28945810 http://dx.doi.org/10.1371/journal.pone.0185222 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Sirenko, Syevda G. Yang, Dongmei Maltseva, Larissa A. Kim, Mary S. Lakatta, Edward G. Maltsev, Victor A. Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells |
title | Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells |
title_full | Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells |
title_fullStr | Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells |
title_full_unstemmed | Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells |
title_short | Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells |
title_sort | spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612473/ https://www.ncbi.nlm.nih.gov/pubmed/28945810 http://dx.doi.org/10.1371/journal.pone.0185222 |
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