This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 104/6/787    most recent CIRCRESAHA.108.193334v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Iribe, G. Articles by Kohl, P. Search for Related Content PubMed PubMed Citation Articles by Iribe, G. Articles by Kohl, P. Related Collections Structure Arrythmias-basic studies Calcium cycling/excitation-contraction coupling Imaging Ion channels/membrane transport Related Article

(Circulation Research. 2009;104:787.)
© 2009 American Heart Association, Inc.

Cellular Biology

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

From the Cardiac MEF Group (G.I., P.C., C.B., F.M., R.A.B.B., A.G., P.K.), Department of Physiology, Anatomy and Genetics, Oxford, UK; School of Nursing (C.W.W.), University of Maryland, Baltimore; Boulder Laboratory for 3-D Electron Microscopy of Cells (M.K.M., A.H.), Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder; and Medical Biotechnology Center (W.J.L.), University of Maryland Biotechnology Institute, Baltimore. Present address for G.I.: Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Correspondence to Dr Peter Kohl, University of Oxford, Department of Physiology, Anatomy and Genetics, Parks Road, Oxford OX1 3PT, United Kingdom. E-mail peter.kohl{at}dpag.ox.ac.uk

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.

Key Words: mechanoelectric feedback • ryanodine receptor • stretch-activated channel • nitric oxide • electron microscopic tomography

Related Article:

Pulling on the Heart Strings: A New Mechanism Within Starling’s Law of the Heart?

Mark B. Cannell
Circ. Res. 2009 104: 715-716. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				M. Ruiz-Meana, A. Abellan, E. Miro-Casas, E. Agullo, and D. Garcia-Dorado Role of sarcoplasmic reticulum in mitochondrial permeability transition and cardiomyocyte death during reperfusion Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1281 - H1289. [Abstract] [Full Text] [PDF]

				M. B. Cannell Pulling on the Heart Strings: A New Mechanism Within Starling's Law of the Heart? Circ. Res., March 27, 2009; 104(6): 715 - 716. [Full Text] [PDF]