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

Bence Hegyi, László Bárándi, I. Komáromi, Ferenc Papp, Balázs Horváth, J. Magyar, Tamás Bányász, Z. Krasznai, N. Szentandrássy, P. Nánási

Research output: Contribution to journalArticle

13 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 2012

Fingerprint

Tetrodotoxin
Cardiac Myocytes
Canidae
Clamping devices
Nisoldipine
Electric potential
Action Potentials
Nerve Tissue
Dermatoglyphics
Patch-Clamp Techniques
Muscle
Skeletal Muscle
Tissue
Calcium
Kinetics
Proteins

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

Cite this

Tetrodotoxin blocks L-type Ca 2+ channels in canine ventricular cardiomyocytes. / Hegyi, Bence; Bárándi, László; Komáromi, I.; Papp, Ferenc; Horváth, Balázs; Magyar, J.; Bányász, Tamás; Krasznai, Z.; Szentandrássy, N.; Nánási, P.

In: Pflugers Archiv European Journal of Physiology, Vol. 464, No. 2, 08.2012, p. 167-174.

Research output: Contribution to journalArticle

Hegyi, Bence ; Bárándi, László ; Komáromi, I. ; Papp, Ferenc ; Horváth, Balázs ; Magyar, J. ; Bányász, Tamás ; Krasznai, Z. ; Szentandrássy, N. ; Nánási, P. / Tetrodotoxin blocks L-type Ca 2+ channels in canine ventricular cardiomyocytes. In: Pflugers Archiv European Journal of Physiology. 2012 ; Vol. 464, No. 2. pp. 167-174.
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