Residual sarcoplasmic reticulum $ Ca^{2+} $ concentration after $ Ca^{2+} $ release in skeletal myofibers from young adult and old mice
Abstract Contrasting information suggests either almost complete depletion of sarcoplasmic reticulum (SR) $ Ca^{2+} $ or significant residual $ Ca^{2+} $ concentration after prolonged depolarization of the skeletal muscle fiber. The primary obstacle to resolving this controversy is the lack of genet...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Wang, Zhong-Min [verfasserIn] Tang, Shen [verfasserIn] Messi, María Laura [verfasserIn] Yang, Jenny J. [verfasserIn] Delbono, Osvaldo [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2012 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Pflügers Archiv - Berlin : Springer, 1868, 463(2012), 4 vom: 17. Jan., Seite 615-624 |
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| Übergeordnetes Werk: |
volume:463 ; year:2012 ; number:4 ; day:17 ; month:01 ; pages:615-624 |
| Links: |
|---|
| DOI / URN: |
10.1007/s00424-012-1073-3 |
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| Katalog-ID: |
SPR005616905 |
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| 245 | 1 | 0 | |a Residual sarcoplasmic reticulum $ Ca^{2+} $ concentration after $ Ca^{2+} $ release in skeletal myofibers from young adult and old mice |
| 264 | 1 | |c 2012 | |
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| 520 | |a Abstract Contrasting information suggests either almost complete depletion of sarcoplasmic reticulum (SR) $ Ca^{2+} $ or significant residual $ Ca^{2+} $ concentration after prolonged depolarization of the skeletal muscle fiber. The primary obstacle to resolving this controversy is the lack of genetically encoded $ Ca^{2+} $ indicators targeted to the SR that exhibit low-$ Ca^{2+} $ affinity, a fast biosensor: $ Ca^{2+} $ off-rate reaction, and can be expressed in myofibers from adult and older adult mammalian species. This work used the recently designed low-affinity $ Ca^{2+} $ sensor (Kd = 1.66 mM in the myofiber) CatchER (calcium sensor for detecting high concentrations in the ER) targeted to the SR, to investigate whether prolonged skeletal muscle fiber depolarization significantly alters residual SR $ Ca^{2+} $ with aging. We found CatchER a proper tool to investigate SR $ Ca^{2+} $ depletion in young adult and older adult mice, consistently tracking SR luminal $ Ca^{2+} $ release in response to brief and repetitive stimulation. We evoked SR $ Ca^{2+} $ release in whole-cell voltage-clamped flexor digitorum brevis muscle fibers from young and old FVB mice and tested the maximal SR $ Ca^{2+} $ release by directly activating the ryanodine receptor (RyR1) with 4-chloro-m-cresol in the same myofibers. Here, we report for the first time that the $ Ca^{2+} $ remaining in the SR after prolonged depolarization (2 s) in myofibers from aging (~220 μM) was larger than young (~132 μM) mice. These experiments indicate that SR $ Ca^{2+} $ is far from fully depleted under physiological conditions throughout life, and support the concept of excitation–contraction uncoupling in functional senescent myofibers. | ||
| 650 | 4 | |a Skeletal muscle |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Calcium sensor |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a CatchER |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Sarcoplasmic reticulum |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Aging |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Tang, Shen |e verfasserin |4 aut | |
| 700 | 1 | |a Messi, María Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jenny J. |e verfasserin |4 aut | |
| 700 | 1 | |a Delbono, Osvaldo |e verfasserin |4 aut | |
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10.1007/s00424-012-1073-3 doi (DE-627)SPR005616905 (SPR)s00424-012-1073-3-e DE-627 ger DE-627 rakwb eng 610 ASE 610 590 ASE 42.63 bkl 44.37 bkl Wang, Zhong-Min verfasserin aut Residual sarcoplasmic reticulum $ Ca^{2+} $ concentration after $ Ca^{2+} $ release in skeletal myofibers from young adult and old mice 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Contrasting information suggests either almost complete depletion of sarcoplasmic reticulum (SR) $ Ca^{2+} $ or significant residual $ Ca^{2+} $ concentration after prolonged depolarization of the skeletal muscle fiber. The primary obstacle to resolving this controversy is the lack of genetically encoded $ Ca^{2+} $ indicators targeted to the SR that exhibit low-$ Ca^{2+} $ affinity, a fast biosensor: $ Ca^{2+} $ off-rate reaction, and can be expressed in myofibers from adult and older adult mammalian species. This work used the recently designed low-affinity $ Ca^{2+} $ sensor (Kd = 1.66 mM in the myofiber) CatchER (calcium sensor for detecting high concentrations in the ER) targeted to the SR, to investigate whether prolonged skeletal muscle fiber depolarization significantly alters residual SR $ Ca^{2+} $ with aging. We found CatchER a proper tool to investigate SR $ Ca^{2+} $ depletion in young adult and older adult mice, consistently tracking SR luminal $ Ca^{2+} $ release in response to brief and repetitive stimulation. We evoked SR $ Ca^{2+} $ release in whole-cell voltage-clamped flexor digitorum brevis muscle fibers from young and old FVB mice and tested the maximal SR $ Ca^{2+} $ release by directly activating the ryanodine receptor (RyR1) with 4-chloro-m-cresol in the same myofibers. Here, we report for the first time that the $ Ca^{2+} $ remaining in the SR after prolonged depolarization (2 s) in myofibers from aging (~220 μM) was larger than young (~132 μM) mice. These experiments indicate that SR $ Ca^{2+} $ is far from fully depleted under physiological conditions throughout life, and support the concept of excitation–contraction uncoupling in functional senescent myofibers. Skeletal muscle (dpeaa)DE-He213 Calcium sensor (dpeaa)DE-He213 CatchER (dpeaa)DE-He213 Sarcoplasmic reticulum (dpeaa)DE-He213 Aging (dpeaa)DE-He213 Tang, Shen verfasserin aut Messi, María Laura verfasserin aut Yang, Jenny J. verfasserin aut Delbono, Osvaldo verfasserin aut Enthalten in Pflügers Archiv Berlin : Springer, 1868 463(2012), 4 vom: 17. Jan., Seite 615-624 (DE-627)25463897X (DE-600)1463014-X 1432-2013 nnns volume:463 year:2012 number:4 day:17 month:01 pages:615-624 https://dx.doi.org/10.1007/s00424-012-1073-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.63 ASE 44.37 ASE AR 463 2012 4 17 01 615-624 |
| spelling |
10.1007/s00424-012-1073-3 doi (DE-627)SPR005616905 (SPR)s00424-012-1073-3-e DE-627 ger DE-627 rakwb eng 610 ASE 610 590 ASE 42.63 bkl 44.37 bkl Wang, Zhong-Min verfasserin aut Residual sarcoplasmic reticulum $ Ca^{2+} $ concentration after $ Ca^{2+} $ release in skeletal myofibers from young adult and old mice 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Contrasting information suggests either almost complete depletion of sarcoplasmic reticulum (SR) $ Ca^{2+} $ or significant residual $ Ca^{2+} $ concentration after prolonged depolarization of the skeletal muscle fiber. The primary obstacle to resolving this controversy is the lack of genetically encoded $ Ca^{2+} $ indicators targeted to the SR that exhibit low-$ Ca^{2+} $ affinity, a fast biosensor: $ Ca^{2+} $ off-rate reaction, and can be expressed in myofibers from adult and older adult mammalian species. This work used the recently designed low-affinity $ Ca^{2+} $ sensor (Kd = 1.66 mM in the myofiber) CatchER (calcium sensor for detecting high concentrations in the ER) targeted to the SR, to investigate whether prolonged skeletal muscle fiber depolarization significantly alters residual SR $ Ca^{2+} $ with aging. We found CatchER a proper tool to investigate SR $ Ca^{2+} $ depletion in young adult and older adult mice, consistently tracking SR luminal $ Ca^{2+} $ release in response to brief and repetitive stimulation. We evoked SR $ Ca^{2+} $ release in whole-cell voltage-clamped flexor digitorum brevis muscle fibers from young and old FVB mice and tested the maximal SR $ Ca^{2+} $ release by directly activating the ryanodine receptor (RyR1) with 4-chloro-m-cresol in the same myofibers. Here, we report for the first time that the $ Ca^{2+} $ remaining in the SR after prolonged depolarization (2 s) in myofibers from aging (~220 μM) was larger than young (~132 μM) mice. These experiments indicate that SR $ Ca^{2+} $ is far from fully depleted under physiological conditions throughout life, and support the concept of excitation–contraction uncoupling in functional senescent myofibers. Skeletal muscle (dpeaa)DE-He213 Calcium sensor (dpeaa)DE-He213 CatchER (dpeaa)DE-He213 Sarcoplasmic reticulum (dpeaa)DE-He213 Aging (dpeaa)DE-He213 Tang, Shen verfasserin aut Messi, María Laura verfasserin aut Yang, Jenny J. verfasserin aut Delbono, Osvaldo verfasserin aut Enthalten in Pflügers Archiv Berlin : Springer, 1868 463(2012), 4 vom: 17. Jan., Seite 615-624 (DE-627)25463897X (DE-600)1463014-X 1432-2013 nnns volume:463 year:2012 number:4 day:17 month:01 pages:615-624 https://dx.doi.org/10.1007/s00424-012-1073-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.63 ASE 44.37 ASE AR 463 2012 4 17 01 615-624 |
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10.1007/s00424-012-1073-3 doi (DE-627)SPR005616905 (SPR)s00424-012-1073-3-e DE-627 ger DE-627 rakwb eng 610 ASE 610 590 ASE 42.63 bkl 44.37 bkl Wang, Zhong-Min verfasserin aut Residual sarcoplasmic reticulum $ Ca^{2+} $ concentration after $ Ca^{2+} $ release in skeletal myofibers from young adult and old mice 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Contrasting information suggests either almost complete depletion of sarcoplasmic reticulum (SR) $ Ca^{2+} $ or significant residual $ Ca^{2+} $ concentration after prolonged depolarization of the skeletal muscle fiber. The primary obstacle to resolving this controversy is the lack of genetically encoded $ Ca^{2+} $ indicators targeted to the SR that exhibit low-$ Ca^{2+} $ affinity, a fast biosensor: $ Ca^{2+} $ off-rate reaction, and can be expressed in myofibers from adult and older adult mammalian species. This work used the recently designed low-affinity $ Ca^{2+} $ sensor (Kd = 1.66 mM in the myofiber) CatchER (calcium sensor for detecting high concentrations in the ER) targeted to the SR, to investigate whether prolonged skeletal muscle fiber depolarization significantly alters residual SR $ Ca^{2+} $ with aging. We found CatchER a proper tool to investigate SR $ Ca^{2+} $ depletion in young adult and older adult mice, consistently tracking SR luminal $ Ca^{2+} $ release in response to brief and repetitive stimulation. We evoked SR $ Ca^{2+} $ release in whole-cell voltage-clamped flexor digitorum brevis muscle fibers from young and old FVB mice and tested the maximal SR $ Ca^{2+} $ release by directly activating the ryanodine receptor (RyR1) with 4-chloro-m-cresol in the same myofibers. Here, we report for the first time that the $ Ca^{2+} $ remaining in the SR after prolonged depolarization (2 s) in myofibers from aging (~220 μM) was larger than young (~132 μM) mice. These experiments indicate that SR $ Ca^{2+} $ is far from fully depleted under physiological conditions throughout life, and support the concept of excitation–contraction uncoupling in functional senescent myofibers. Skeletal muscle (dpeaa)DE-He213 Calcium sensor (dpeaa)DE-He213 CatchER (dpeaa)DE-He213 Sarcoplasmic reticulum (dpeaa)DE-He213 Aging (dpeaa)DE-He213 Tang, Shen verfasserin aut Messi, María Laura verfasserin aut Yang, Jenny J. verfasserin aut Delbono, Osvaldo verfasserin aut Enthalten in Pflügers Archiv Berlin : Springer, 1868 463(2012), 4 vom: 17. Jan., Seite 615-624 (DE-627)25463897X (DE-600)1463014-X 1432-2013 nnns volume:463 year:2012 number:4 day:17 month:01 pages:615-624 https://dx.doi.org/10.1007/s00424-012-1073-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.63 ASE 44.37 ASE AR 463 2012 4 17 01 615-624 |
| allfieldsGer |
10.1007/s00424-012-1073-3 doi (DE-627)SPR005616905 (SPR)s00424-012-1073-3-e DE-627 ger DE-627 rakwb eng 610 ASE 610 590 ASE 42.63 bkl 44.37 bkl Wang, Zhong-Min verfasserin aut Residual sarcoplasmic reticulum $ Ca^{2+} $ concentration after $ Ca^{2+} $ release in skeletal myofibers from young adult and old mice 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Contrasting information suggests either almost complete depletion of sarcoplasmic reticulum (SR) $ Ca^{2+} $ or significant residual $ Ca^{2+} $ concentration after prolonged depolarization of the skeletal muscle fiber. The primary obstacle to resolving this controversy is the lack of genetically encoded $ Ca^{2+} $ indicators targeted to the SR that exhibit low-$ Ca^{2+} $ affinity, a fast biosensor: $ Ca^{2+} $ off-rate reaction, and can be expressed in myofibers from adult and older adult mammalian species. This work used the recently designed low-affinity $ Ca^{2+} $ sensor (Kd = 1.66 mM in the myofiber) CatchER (calcium sensor for detecting high concentrations in the ER) targeted to the SR, to investigate whether prolonged skeletal muscle fiber depolarization significantly alters residual SR $ Ca^{2+} $ with aging. We found CatchER a proper tool to investigate SR $ Ca^{2+} $ depletion in young adult and older adult mice, consistently tracking SR luminal $ Ca^{2+} $ release in response to brief and repetitive stimulation. We evoked SR $ Ca^{2+} $ release in whole-cell voltage-clamped flexor digitorum brevis muscle fibers from young and old FVB mice and tested the maximal SR $ Ca^{2+} $ release by directly activating the ryanodine receptor (RyR1) with 4-chloro-m-cresol in the same myofibers. Here, we report for the first time that the $ Ca^{2+} $ remaining in the SR after prolonged depolarization (2 s) in myofibers from aging (~220 μM) was larger than young (~132 μM) mice. These experiments indicate that SR $ Ca^{2+} $ is far from fully depleted under physiological conditions throughout life, and support the concept of excitation–contraction uncoupling in functional senescent myofibers. Skeletal muscle (dpeaa)DE-He213 Calcium sensor (dpeaa)DE-He213 CatchER (dpeaa)DE-He213 Sarcoplasmic reticulum (dpeaa)DE-He213 Aging (dpeaa)DE-He213 Tang, Shen verfasserin aut Messi, María Laura verfasserin aut Yang, Jenny J. verfasserin aut Delbono, Osvaldo verfasserin aut Enthalten in Pflügers Archiv Berlin : Springer, 1868 463(2012), 4 vom: 17. Jan., Seite 615-624 (DE-627)25463897X (DE-600)1463014-X 1432-2013 nnns volume:463 year:2012 number:4 day:17 month:01 pages:615-624 https://dx.doi.org/10.1007/s00424-012-1073-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.63 ASE 44.37 ASE AR 463 2012 4 17 01 615-624 |
| allfieldsSound |
10.1007/s00424-012-1073-3 doi (DE-627)SPR005616905 (SPR)s00424-012-1073-3-e DE-627 ger DE-627 rakwb eng 610 ASE 610 590 ASE 42.63 bkl 44.37 bkl Wang, Zhong-Min verfasserin aut Residual sarcoplasmic reticulum $ Ca^{2+} $ concentration after $ Ca^{2+} $ release in skeletal myofibers from young adult and old mice 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Contrasting information suggests either almost complete depletion of sarcoplasmic reticulum (SR) $ Ca^{2+} $ or significant residual $ Ca^{2+} $ concentration after prolonged depolarization of the skeletal muscle fiber. The primary obstacle to resolving this controversy is the lack of genetically encoded $ Ca^{2+} $ indicators targeted to the SR that exhibit low-$ Ca^{2+} $ affinity, a fast biosensor: $ Ca^{2+} $ off-rate reaction, and can be expressed in myofibers from adult and older adult mammalian species. This work used the recently designed low-affinity $ Ca^{2+} $ sensor (Kd = 1.66 mM in the myofiber) CatchER (calcium sensor for detecting high concentrations in the ER) targeted to the SR, to investigate whether prolonged skeletal muscle fiber depolarization significantly alters residual SR $ Ca^{2+} $ with aging. We found CatchER a proper tool to investigate SR $ Ca^{2+} $ depletion in young adult and older adult mice, consistently tracking SR luminal $ Ca^{2+} $ release in response to brief and repetitive stimulation. We evoked SR $ Ca^{2+} $ release in whole-cell voltage-clamped flexor digitorum brevis muscle fibers from young and old FVB mice and tested the maximal SR $ Ca^{2+} $ release by directly activating the ryanodine receptor (RyR1) with 4-chloro-m-cresol in the same myofibers. Here, we report for the first time that the $ Ca^{2+} $ remaining in the SR after prolonged depolarization (2 s) in myofibers from aging (~220 μM) was larger than young (~132 μM) mice. These experiments indicate that SR $ Ca^{2+} $ is far from fully depleted under physiological conditions throughout life, and support the concept of excitation–contraction uncoupling in functional senescent myofibers. Skeletal muscle (dpeaa)DE-He213 Calcium sensor (dpeaa)DE-He213 CatchER (dpeaa)DE-He213 Sarcoplasmic reticulum (dpeaa)DE-He213 Aging (dpeaa)DE-He213 Tang, Shen verfasserin aut Messi, María Laura verfasserin aut Yang, Jenny J. verfasserin aut Delbono, Osvaldo verfasserin aut Enthalten in Pflügers Archiv Berlin : Springer, 1868 463(2012), 4 vom: 17. Jan., Seite 615-624 (DE-627)25463897X (DE-600)1463014-X 1432-2013 nnns volume:463 year:2012 number:4 day:17 month:01 pages:615-624 https://dx.doi.org/10.1007/s00424-012-1073-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.63 ASE 44.37 ASE AR 463 2012 4 17 01 615-624 |
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English |
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Enthalten in Pflügers Archiv 463(2012), 4 vom: 17. Jan., Seite 615-624 volume:463 year:2012 number:4 day:17 month:01 pages:615-624 |
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Enthalten in Pflügers Archiv 463(2012), 4 vom: 17. Jan., Seite 615-624 volume:463 year:2012 number:4 day:17 month:01 pages:615-624 |
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findex.gbv.de |
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Skeletal muscle Calcium sensor CatchER Sarcoplasmic reticulum Aging |
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Wang, Zhong-Min @@aut@@ Tang, Shen @@aut@@ Messi, María Laura @@aut@@ Yang, Jenny J. @@aut@@ Delbono, Osvaldo @@aut@@ |
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2012-01-17T00:00:00Z |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR005616905</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519154034.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201002s2012 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s00424-012-1073-3</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR005616905</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s00424-012-1073-3-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="a">590</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">42.63</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.37</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Wang, Zhong-Min</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Residual sarcoplasmic reticulum $ Ca^{2+} $ concentration after $ Ca^{2+} $ release in skeletal myofibers from young adult and old mice</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2012</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Contrasting information suggests either almost complete depletion of sarcoplasmic reticulum (SR) $ Ca^{2+} $ or significant residual $ Ca^{2+} $ concentration after prolonged depolarization of the skeletal muscle fiber. The primary obstacle to resolving this controversy is the lack of genetically encoded $ Ca^{2+} $ indicators targeted to the SR that exhibit low-$ Ca^{2+} $ affinity, a fast biosensor: $ Ca^{2+} $ off-rate reaction, and can be expressed in myofibers from adult and older adult mammalian species. This work used the recently designed low-affinity $ Ca^{2+} $ sensor (Kd = 1.66 mM in the myofiber) CatchER (calcium sensor for detecting high concentrations in the ER) targeted to the SR, to investigate whether prolonged skeletal muscle fiber depolarization significantly alters residual SR $ Ca^{2+} $ with aging. We found CatchER a proper tool to investigate SR $ Ca^{2+} $ depletion in young adult and older adult mice, consistently tracking SR luminal $ Ca^{2+} $ release in response to brief and repetitive stimulation. We evoked SR $ Ca^{2+} $ release in whole-cell voltage-clamped flexor digitorum brevis muscle fibers from young and old FVB mice and tested the maximal SR $ Ca^{2+} $ release by directly activating the ryanodine receptor (RyR1) with 4-chloro-m-cresol in the same myofibers. Here, we report for the first time that the $ Ca^{2+} $ remaining in the SR after prolonged depolarization (2 s) in myofibers from aging (~220 μM) was larger than young (~132 μM) mice. These experiments indicate that SR $ Ca^{2+} $ is far from fully depleted under physiological conditions throughout life, and support the concept of excitation–contraction uncoupling in functional senescent myofibers.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Skeletal muscle</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Calcium sensor</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">CatchER</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Sarcoplasmic reticulum</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Aging</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tang, Shen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Messi, María Laura</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yang, Jenny J.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Delbono, Osvaldo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Pflügers Archiv</subfield><subfield code="d">Berlin : Springer, 1868</subfield><subfield code="g">463(2012), 4 vom: 17. 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|
| author |
Wang, Zhong-Min |
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Wang, Zhong-Min ddc 610 bkl 42.63 bkl 44.37 misc Skeletal muscle misc Calcium sensor misc CatchER misc Sarcoplasmic reticulum misc Aging Residual sarcoplasmic reticulum $ Ca^{2+} $ concentration after $ Ca^{2+} $ release in skeletal myofibers from young adult and old mice |
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610 ASE 610 590 ASE 42.63 bkl 44.37 bkl Residual sarcoplasmic reticulum $ Ca^{2+} $ concentration after $ Ca^{2+} $ release in skeletal myofibers from young adult and old mice Skeletal muscle (dpeaa)DE-He213 Calcium sensor (dpeaa)DE-He213 CatchER (dpeaa)DE-He213 Sarcoplasmic reticulum (dpeaa)DE-He213 Aging (dpeaa)DE-He213 |
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ddc 610 bkl 42.63 bkl 44.37 misc Skeletal muscle misc Calcium sensor misc CatchER misc Sarcoplasmic reticulum misc Aging |
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ddc 610 bkl 42.63 bkl 44.37 misc Skeletal muscle misc Calcium sensor misc CatchER misc Sarcoplasmic reticulum misc Aging |
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Residual sarcoplasmic reticulum $ Ca^{2+} $ concentration after $ Ca^{2+} $ release in skeletal myofibers from young adult and old mice |
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Residual sarcoplasmic reticulum $ Ca^{2+} $ concentration after $ Ca^{2+} $ release in skeletal myofibers from young adult and old mice |
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Wang, Zhong-Min |
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Pflügers Archiv |
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2012 |
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Wang, Zhong-Min Tang, Shen Messi, María Laura Yang, Jenny J. Delbono, Osvaldo |
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Elektronische Aufsätze |
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Wang, Zhong-Min |
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residual sarcoplasmic reticulum $ ca^{2+} $ concentration after $ ca^{2+} $ release in skeletal myofibers from young adult and old mice |
| title_auth |
Residual sarcoplasmic reticulum $ Ca^{2+} $ concentration after $ Ca^{2+} $ release in skeletal myofibers from young adult and old mice |
| abstract |
Abstract Contrasting information suggests either almost complete depletion of sarcoplasmic reticulum (SR) $ Ca^{2+} $ or significant residual $ Ca^{2+} $ concentration after prolonged depolarization of the skeletal muscle fiber. The primary obstacle to resolving this controversy is the lack of genetically encoded $ Ca^{2+} $ indicators targeted to the SR that exhibit low-$ Ca^{2+} $ affinity, a fast biosensor: $ Ca^{2+} $ off-rate reaction, and can be expressed in myofibers from adult and older adult mammalian species. This work used the recently designed low-affinity $ Ca^{2+} $ sensor (Kd = 1.66 mM in the myofiber) CatchER (calcium sensor for detecting high concentrations in the ER) targeted to the SR, to investigate whether prolonged skeletal muscle fiber depolarization significantly alters residual SR $ Ca^{2+} $ with aging. We found CatchER a proper tool to investigate SR $ Ca^{2+} $ depletion in young adult and older adult mice, consistently tracking SR luminal $ Ca^{2+} $ release in response to brief and repetitive stimulation. We evoked SR $ Ca^{2+} $ release in whole-cell voltage-clamped flexor digitorum brevis muscle fibers from young and old FVB mice and tested the maximal SR $ Ca^{2+} $ release by directly activating the ryanodine receptor (RyR1) with 4-chloro-m-cresol in the same myofibers. Here, we report for the first time that the $ Ca^{2+} $ remaining in the SR after prolonged depolarization (2 s) in myofibers from aging (~220 μM) was larger than young (~132 μM) mice. These experiments indicate that SR $ Ca^{2+} $ is far from fully depleted under physiological conditions throughout life, and support the concept of excitation–contraction uncoupling in functional senescent myofibers. |
| abstractGer |
Abstract Contrasting information suggests either almost complete depletion of sarcoplasmic reticulum (SR) $ Ca^{2+} $ or significant residual $ Ca^{2+} $ concentration after prolonged depolarization of the skeletal muscle fiber. The primary obstacle to resolving this controversy is the lack of genetically encoded $ Ca^{2+} $ indicators targeted to the SR that exhibit low-$ Ca^{2+} $ affinity, a fast biosensor: $ Ca^{2+} $ off-rate reaction, and can be expressed in myofibers from adult and older adult mammalian species. This work used the recently designed low-affinity $ Ca^{2+} $ sensor (Kd = 1.66 mM in the myofiber) CatchER (calcium sensor for detecting high concentrations in the ER) targeted to the SR, to investigate whether prolonged skeletal muscle fiber depolarization significantly alters residual SR $ Ca^{2+} $ with aging. We found CatchER a proper tool to investigate SR $ Ca^{2+} $ depletion in young adult and older adult mice, consistently tracking SR luminal $ Ca^{2+} $ release in response to brief and repetitive stimulation. We evoked SR $ Ca^{2+} $ release in whole-cell voltage-clamped flexor digitorum brevis muscle fibers from young and old FVB mice and tested the maximal SR $ Ca^{2+} $ release by directly activating the ryanodine receptor (RyR1) with 4-chloro-m-cresol in the same myofibers. Here, we report for the first time that the $ Ca^{2+} $ remaining in the SR after prolonged depolarization (2 s) in myofibers from aging (~220 μM) was larger than young (~132 μM) mice. These experiments indicate that SR $ Ca^{2+} $ is far from fully depleted under physiological conditions throughout life, and support the concept of excitation–contraction uncoupling in functional senescent myofibers. |
| abstract_unstemmed |
Abstract Contrasting information suggests either almost complete depletion of sarcoplasmic reticulum (SR) $ Ca^{2+} $ or significant residual $ Ca^{2+} $ concentration after prolonged depolarization of the skeletal muscle fiber. The primary obstacle to resolving this controversy is the lack of genetically encoded $ Ca^{2+} $ indicators targeted to the SR that exhibit low-$ Ca^{2+} $ affinity, a fast biosensor: $ Ca^{2+} $ off-rate reaction, and can be expressed in myofibers from adult and older adult mammalian species. This work used the recently designed low-affinity $ Ca^{2+} $ sensor (Kd = 1.66 mM in the myofiber) CatchER (calcium sensor for detecting high concentrations in the ER) targeted to the SR, to investigate whether prolonged skeletal muscle fiber depolarization significantly alters residual SR $ Ca^{2+} $ with aging. We found CatchER a proper tool to investigate SR $ Ca^{2+} $ depletion in young adult and older adult mice, consistently tracking SR luminal $ Ca^{2+} $ release in response to brief and repetitive stimulation. We evoked SR $ Ca^{2+} $ release in whole-cell voltage-clamped flexor digitorum brevis muscle fibers from young and old FVB mice and tested the maximal SR $ Ca^{2+} $ release by directly activating the ryanodine receptor (RyR1) with 4-chloro-m-cresol in the same myofibers. Here, we report for the first time that the $ Ca^{2+} $ remaining in the SR after prolonged depolarization (2 s) in myofibers from aging (~220 μM) was larger than young (~132 μM) mice. These experiments indicate that SR $ Ca^{2+} $ is far from fully depleted under physiological conditions throughout life, and support the concept of excitation–contraction uncoupling in functional senescent myofibers. |
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Residual sarcoplasmic reticulum $ Ca^{2+} $ concentration after $ Ca^{2+} $ release in skeletal myofibers from young adult and old mice |
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https://dx.doi.org/10.1007/s00424-012-1073-3 |
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| score |
7.400094 |