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The Effect of Substrate Stiffness on Cardiomyocyte Action Potentials

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Abstract

The stiffness of myocardial tissue changes significantly at birth and during neonatal development, concurrent with significant changes in contractile and electrical maturation of cardiomyocytes. Previous studies by our group have shown that cardiomyocytes generate maximum contractile force when cultured on a substrate with a stiffness approximating native cardiac tissue. However, effects of substrate stiffness on the electrophysiology and ion currents in cardiomyocytes have not been fully characterized. In this study, neonatal rat ventricular myocytes were cultured on the surface of flat polyacrylamide hydrogels with elastic moduli ranging from 1 to 25 kPa. Using whole-cell patch clamping, action potentials and L-type calcium currents were recorded. Cardiomyocytes cultured on hydrogels with a 9 kPa elastic modulus, similar to that of native myocardium, had the longest action potential duration. Additionally, the voltage at maximum calcium flux significantly decreased in cardiomyocytes on hydrogels with an elastic modulus higher than 9 kPa, and the mean inactivation voltage decreased with increasing stiffness. Interestingly, the expression of the L-type calcium channel subunit α gene and channel localization did not change with stiffness. Substrate stiffness significantly affects action potential length and calcium flux in cultured neonatal rat cardiomyocytes in a manner that may be unrelated to calcium channel expression. These results may explain functional differences in cardiomyocytes resulting from changes in the elastic modulus of the extracellular matrix, as observed during embryonic development, in ischemic regions of the heart after myocardial infarction, and during dilated cardiomyopathy.

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Acknowledgments

Funding for this research was provided by the NIH/NHLBI (1R21HL110330-01 to JGJ) and by Texas Children’s Hospital.

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Authors and Affiliations

  1. Rice University Department of Bioengineering, Houston, TX, USA

    Sean D. Boothe, Jackson D. Myers, Seokwon Pok & Jeffrey G. Jacot

  2. Texas Children’s Hospital, Division of Congenital Heart Surgery, Houston, TX, USA

    Seokwon Pok, Raymond M Nieto & Jeffrey G. Jacot

  3. Texas Heart Institute/St. Luke’s Hospital, Houston, TX, USA

    Junping Sun, Yutao Xi & Jie Cheng

  4. Section of Cardiology, University of Texas School of Medicine at Houston, Houston, TX, USA

    Jie Cheng

Authors
  1. Sean D. Boothe
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  2. Jackson D. Myers
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  3. Seokwon Pok
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  4. Junping Sun
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  5. Yutao Xi
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  6. Raymond M Nieto
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  8. Jeffrey G. Jacot
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Correspondence to Jeffrey G. Jacot.

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Boothe, S.D., Myers, J.D., Pok, S. et al. The Effect of Substrate Stiffness on Cardiomyocyte Action Potentials. Cell Biochem Biophys 74, 527–535 (2016). https://doi.org/10.1007/s12013-016-0758-1

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  • DOI: https://doi.org/10.1007/s12013-016-0758-1

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