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Tetrodotoxin blocks L-type Ca2+ channels in canine ventricular cardiomyocytes

  • Ion channels, receptors and transporters
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Abstract

Tetrodotoxin (TTX) is believed to be the most selective inhibitor of voltage-gated fast Na+ channels in excitable tissues, including nerve, skeletal muscle, and heart, although TTX sensitivity of the latter is lower than the former by at least three orders of magnitude. In the present study, the TTX sensitivity of L-type Ca2+ current (I Ca) was studied in isolated canine ventricular cells using conventional voltage clamp and action potential voltage clamp techniques. TTX was found to block I Ca in a reversible manner without altering inactivation kinetics of I Ca. Fitting results to the Hill equation, an IC50 value of 55 ± 2 μM was obtained with a Hill coefficient of unity (1.0 ± s0.04). The current was fully abolished by 1 μM nisoldipine, indicating that it was really I Ca. Under action potential voltage clamp conditions, the TTX-sensitive current displayed the typical fingerprint of I Ca, which was absent in the presence of nisoldipine. Stick-and-ball models for Cav1.2 and Nav1.5 channel proteins were constructed to explain the differences observed between action of TTX on cardiac I Ca and I Na. This is the first report demonstrating TTX to interact with L-type calcium current in the heart.

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Acknowledgments

Financial support for the studies was provided by grants from the Hungarian Research Fund (OTKA-K100151, OTKA-PD101171, OTKA-K101196, and CNK-77855). The authors thank Mrs. Vighné Katalin Horváth for excellent technical assistance.

Conflict of interest

The authors declare that that they have no conflict of interest.

Author Note

The experiments comply with the current laws of Hungary.

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Authors and Affiliations

  1. Department of Physiology, University of Debrecen, P.O. Box 22, 4012, Debrecen, Hungary

    Bence Hegyi, László Bárándi, Balázs Horváth, János Magyar, Tamás Bányász, Norbert Szentandrássy & Péter P. Nánási

  2. Clinical Research Center and Thrombosis Haemostasis and Vascular Biology Research Group of the Hungarian Academy of Sciences, University of Debrecen, P.O. Box 40, 4012, Debrecen, Hungary

    István Komáromi

  3. Department of Biophysics and Cell Biology, Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences, University of Debrecen, P.O. Box 39, 4012, Debrecen, Hungary

    Ferenc Papp

  4. Department of Biophysics and Cell Biology, University of Debrecen, P.O. Box 39, 4012, Debrecen, Hungary

    Zoltán Krasznai

Authors
  1. Bence Hegyi
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  2. László Bárándi
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  3. István Komáromi
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  4. Ferenc Papp
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  5. Balázs Horváth
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  6. János Magyar
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  7. Tamás Bányász
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  8. Zoltán Krasznai
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  9. Norbert Szentandrássy
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  10. Péter P. Nánási
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Correspondence to Péter P. Nánási.

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Hegyi, B., Bárándi, L., Komáromi, I. et al. Tetrodotoxin blocks L-type Ca2+ channels in canine ventricular cardiomyocytes. Pflugers Arch - Eur J Physiol 464, 167–174 (2012). https://doi.org/10.1007/s00424-012-1114-y

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  • DOI: https://doi.org/10.1007/s00424-012-1114-y

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