Axial stretch of rat single ventricular cardiomyocytes causes an acute and transient increase in Ca2+ spark rate

Gentaro Iribe, Christopher W. Ward, Patrizia Camelliti, Christian Bollensdorff, Fleur Mason, Rebecca A B Burton, Alan Garny, Mary K. Morphew, Andreas Hoenger, W. Jonathan Lederer, Peter Kohl

Research output: Contribution to journalArticle

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Abstract

We investigate acute effects of axial stretch, applied by carbon fibers (CFs), on diastolic Ca2+ spark rate in rat isolated cardiomyocytes. CFs were attached either to both cell ends (to maximize the stretched region), or to the center and one end of the cell (to compare responses in stretched and nonstretched half-cells). Sarcomere length was increased by 8.01±0.94% in the stretched cell fraction, and time series of XY confocal images were recorded to monitor diastolic Ca2+ spark frequency and dynamics. Whole-cell stretch causes an acute increase of Ca2+ spark rate (to 130.7±6.4%) within 5 seconds, followed by a return to near background levels (to 104.4±5.1%) within 1 minute of sustained distension. Spark rate increased only in the stretched cell region, without significant differences in spark amplitude, time to peak, and decay time constants of sparks in stretched and nonstretched areas. Block of stretch-activated ion channels (2 μmol/L GsMTx-4), perfusion with Na+/Ca2+-free solution, and block of nitric oxide synthesis (1 mmol/L L-NAME) all had no effect on the stretch-induced acute increase in Ca2+ spark rate. Conversely, interference with cytoskeletal integrity (2 hours of 10 μmol/L colchicine) abolished the response. Subsequent electron microscopic tomography confirmed the close approximation of microtubules with the T-tubular- sarcoplasmic reticulum complex (to within ≈10-8m). In conclusion, axial stretch of rat cardiomyocytes acutely and transiently increases sarcoplasmic reticulum Ca2+ spark rate via a mechanism that is independent of sarcolemmal stretch-activated ion channels, nitric oxide synthesis, or availability of extracellular calcium but that requires cytoskeletal integrity. The potential of microtubule-mediated modulation of ryanodine receptor function warrants further investigation.

Original languageEnglish
Pages (from-to)787-795
Number of pages9
JournalCirculation Research
Volume104
Issue number6
DOIs
Publication statusPublished - Mar 27 2009

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Cardiac Myocytes
Sarcoplasmic Reticulum
Ion Channels
Microtubules
Nitric Oxide
Electron Microscope Tomography
Sarcomeres
Ryanodine Receptor Calcium Release Channel
NG-Nitroarginine Methyl Ester
Colchicine
Perfusion
Calcium

Keywords

  • Electron microscopic tomography
  • Mechanoelectric feedback
  • Nitric oxide
  • Ryanodine receptor
  • Stretch-activated channel

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Iribe, G., Ward, C. W., Camelliti, P., Bollensdorff, C., Mason, F., Burton, R. A. B., ... Kohl, P. (2009). Axial stretch of rat single ventricular cardiomyocytes causes an acute and transient increase in Ca2+ spark rate. Circulation Research, 104(6), 787-795. https://doi.org/10.1161/CIRCRESAHA.108.193334

Axial stretch of rat single ventricular cardiomyocytes causes an acute and transient increase in Ca2+ spark rate. / Iribe, Gentaro; Ward, Christopher W.; Camelliti, Patrizia; Bollensdorff, Christian; Mason, Fleur; Burton, Rebecca A B; Garny, Alan; Morphew, Mary K.; Hoenger, Andreas; Lederer, W. Jonathan; Kohl, Peter.

In: Circulation Research, Vol. 104, No. 6, 27.03.2009, p. 787-795.

Research output: Contribution to journalArticle

Iribe, G, Ward, CW, Camelliti, P, Bollensdorff, C, Mason, F, Burton, RAB, Garny, A, Morphew, MK, Hoenger, A, Lederer, WJ & Kohl, P 2009, 'Axial stretch of rat single ventricular cardiomyocytes causes an acute and transient increase in Ca2+ spark rate', Circulation Research, vol. 104, no. 6, pp. 787-795. https://doi.org/10.1161/CIRCRESAHA.108.193334
Iribe, Gentaro ; Ward, Christopher W. ; Camelliti, Patrizia ; Bollensdorff, Christian ; Mason, Fleur ; Burton, Rebecca A B ; Garny, Alan ; Morphew, Mary K. ; Hoenger, Andreas ; Lederer, W. Jonathan ; Kohl, Peter. / Axial stretch of rat single ventricular cardiomyocytes causes an acute and transient increase in Ca2+ spark rate. In: Circulation Research. 2009 ; Vol. 104, No. 6. pp. 787-795.
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abstract = "We investigate acute effects of axial stretch, applied by carbon fibers (CFs), on diastolic Ca2+ spark rate in rat isolated cardiomyocytes. CFs were attached either to both cell ends (to maximize the stretched region), or to the center and one end of the cell (to compare responses in stretched and nonstretched half-cells). Sarcomere length was increased by 8.01±0.94{\%} in the stretched cell fraction, and time series of XY confocal images were recorded to monitor diastolic Ca2+ spark frequency and dynamics. Whole-cell stretch causes an acute increase of Ca2+ spark rate (to 130.7±6.4{\%}) within 5 seconds, followed by a return to near background levels (to 104.4±5.1{\%}) within 1 minute of sustained distension. Spark rate increased only in the stretched cell region, without significant differences in spark amplitude, time to peak, and decay time constants of sparks in stretched and nonstretched areas. Block of stretch-activated ion channels (2 μmol/L GsMTx-4), perfusion with Na+/Ca2+-free solution, and block of nitric oxide synthesis (1 mmol/L L-NAME) all had no effect on the stretch-induced acute increase in Ca2+ spark rate. Conversely, interference with cytoskeletal integrity (2 hours of 10 μmol/L colchicine) abolished the response. Subsequent electron microscopic tomography confirmed the close approximation of microtubules with the T-tubular- sarcoplasmic reticulum complex (to within ≈10-8m). In conclusion, axial stretch of rat cardiomyocytes acutely and transiently increases sarcoplasmic reticulum Ca2+ spark rate via a mechanism that is independent of sarcolemmal stretch-activated ion channels, nitric oxide synthesis, or availability of extracellular calcium but that requires cytoskeletal integrity. The potential of microtubule-mediated modulation of ryanodine receptor function warrants further investigation.",
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AU - Ward, Christopher W.

AU - Camelliti, Patrizia

AU - Bollensdorff, Christian

AU - Mason, Fleur

AU - Burton, Rebecca A B

AU - Garny, Alan

AU - Morphew, Mary K.

AU - Hoenger, Andreas

AU - Lederer, W. Jonathan

AU - Kohl, Peter

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N2 - We investigate acute effects of axial stretch, applied by carbon fibers (CFs), on diastolic Ca2+ spark rate in rat isolated cardiomyocytes. CFs were attached either to both cell ends (to maximize the stretched region), or to the center and one end of the cell (to compare responses in stretched and nonstretched half-cells). Sarcomere length was increased by 8.01±0.94% in the stretched cell fraction, and time series of XY confocal images were recorded to monitor diastolic Ca2+ spark frequency and dynamics. Whole-cell stretch causes an acute increase of Ca2+ spark rate (to 130.7±6.4%) within 5 seconds, followed by a return to near background levels (to 104.4±5.1%) within 1 minute of sustained distension. Spark rate increased only in the stretched cell region, without significant differences in spark amplitude, time to peak, and decay time constants of sparks in stretched and nonstretched areas. Block of stretch-activated ion channels (2 μmol/L GsMTx-4), perfusion with Na+/Ca2+-free solution, and block of nitric oxide synthesis (1 mmol/L L-NAME) all had no effect on the stretch-induced acute increase in Ca2+ spark rate. Conversely, interference with cytoskeletal integrity (2 hours of 10 μmol/L colchicine) abolished the response. Subsequent electron microscopic tomography confirmed the close approximation of microtubules with the T-tubular- sarcoplasmic reticulum complex (to within ≈10-8m). In conclusion, axial stretch of rat cardiomyocytes acutely and transiently increases sarcoplasmic reticulum Ca2+ spark rate via a mechanism that is independent of sarcolemmal stretch-activated ion channels, nitric oxide synthesis, or availability of extracellular calcium but that requires cytoskeletal integrity. The potential of microtubule-mediated modulation of ryanodine receptor function warrants further investigation.

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KW - Mechanoelectric feedback

KW - Nitric oxide

KW - Ryanodine receptor

KW - Stretch-activated channel

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