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The Effect of Substrate Stiffness on Cardiomyocyte Action Potentials
Sean D Boothe1, Jackson D Myers1, Seokwon Pok1,2
1Rice University Department of Bioengineering, Houston, TX, USA.
Cell Biochemistry and Biophysics
|October 11, 2016
Summary
Substrate stiffness significantly impacts cardiomyocyte electrical activity and calcium currents. Optimal function occurs at 9 kPa, with higher stiffness altering action potential duration and calcium flux, independent of L-type calcium channel expression.
Area of Science:
- Cardiovascular Biology
- Biophysics
- Cellular Electrophysiology
Background:
- Myocardial tissue stiffness changes during neonatal development, affecting cardiomyocyte maturation.
- Previous research linked substrate stiffness to cardiomyocyte contractile force.
- The impact of substrate stiffness on cardiomyocyte electrophysiology remains undercharacterized.
Purpose of the Study:
- To investigate the effects of substrate stiffness on the electrophysiology and L-type calcium currents of neonatal rat ventricular myocytes.
- To determine the relationship between substrate elastic modulus and action potential characteristics and calcium flux.
Main Methods:
- Neonatal rat ventricular myocytes were cultured on polyacrylamide hydrogels with elastic moduli from 1 to 25 kPa.
- Whole-cell patch clamp technique was employed to record action potentials and L-type calcium currents.
- Gene expression and protein localization of the L-type calcium channel subunit α were analyzed.
Main Results:
- Cardiomyocytes on 9 kPa hydrogels (native myocardial stiffness) exhibited the longest action potential duration.
- Higher stiffness (>9 kPa) led to a decreased voltage at maximum calcium flux and a reduced mean inactivation voltage.
- L-type calcium channel gene expression and localization remained unchanged across different stiffness levels.
Conclusions:
- Substrate stiffness significantly modulates action potential duration and calcium flux in cardiomyocytes.
- These effects appear independent of changes in L-type calcium channel expression or localization.
- Findings may explain functional cardiomyocyte variations in development, ischemia, and cardiomyopathy due to extracellular matrix stiffness changes.
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