Tetrodotoxin blocks L-type Ca 2+ channels in canine ventricular cardiomyocytes

Bence Hegyi, László Bárándi, István Komáromi, Ferenc Papp, Balázs Horváth, János Magyar, Tamás Bányász, Zoltán Krasznai, Norbert Szentandrássy, Péter P. Nánási

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16 Citations (Scopus)

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 Ca 2+ 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 IC 50 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.

Original languageEnglish
Pages (from-to)167-174
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Volume464
Issue number2
DOIs
Publication statusPublished - Aug 1 2012

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Keywords

  • Calciumchannels
  • Dog heart
  • Sodium channels
  • Tetrodotoxin
  • Voltage clamp

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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