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Updated: Jun 19, 2026
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Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles
Published on: October 15, 2014
Tubulin polymerization modifies cardiac sodium channel expression and gating
Simona Casini1, Hanno L Tan, Ilker Demirayak
1Department of Clinical and Experimental Cardiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Cardiovascular Research
|October 29, 2009
Summary
The anticancer drug Taxol (TXL) impairs cardiac sodium channel (Na(v)1.5) function and expression by enhancing tubulin polymerization. These effects, particularly on channel inactivation, depend on the beta1-subunit and may contribute to cardiac arrhythmias.
Area of Science:
- Cardiovascular Pharmacology
- Molecular Cardiology
- Cellular Electrophysiology
Background:
- The anticancer drug Taxol (TXL) polymerizes tubulin, potentially affecting cardiac function.
- Reduced function of the human cardiac sodium channel Na(v)1.5 is linked to cardiac arrhythmias.
- The role of tubulin polymerization and beta1-subunit in TXL-induced Na(v)1.5 dysfunction is unclear.
Purpose of the Study:
- To investigate how TXL-induced tubulin polymerization affects Na(v)1.5 function and expression.
- To determine if these effects are mediated by the Na(v)1.5 beta1-subunit.
Main Methods:
- Utilized human embryonic kidney (HEK293) cells and neonatal rat cardiomyocytes (NRCs).
- Expressed Na(v)1.5 alone or with the beta1-subunit (Na(v)1.5 + beta1).
- Assessed sodium current (I(Na)) using patch-clamp, and Na(v)1.5 membrane expression via immunocytochemistry after TXL treatment.
Main Results:
- TXL significantly reduced peak I(Na) amplitude and Na(v)1.5 membrane expression in all cell types.
- TXL accelerated I(Na) decay and impaired slow inactivation of Na(v)1.5 in a beta1-subunit-dependent manner.
- Conversely, TXL did not alter slow inactivation properties of Na(v)1.5 + beta1.
Conclusions:
- Enhanced tubulin polymerization by TXL reduces Na(v)1.5 expression and amplitude independently of the beta1-subunit.
- TXL-induced impairment of I(Na) fast and slow inactivation is dependent on the beta1-subunit.
- These channel alterations may explain TXL-associated cardiac arrhythmias and heart failure.
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