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Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes
11:33

Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes

Published on: March 12, 2013

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

Bence Hegyi1, László Bárándi, István Komáromi

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

Pflugers Archiv : European Journal of Physiology
|May 23, 2012
PubMed

Insights

Tetrodotoxin (TTX) interacts with cardiac L-type calcium channels, contrary to its known effect on sodium channels. This study reveals TTX

Area of Science:

  • Cardiovascular Physiology
  • Molecular Pharmacology
  • Ion Channel Biology

Background:

  • Tetrodotoxin (TTX) is a well-established selective blocker of voltage-gated sodium channels (Nav) in excitable tissues.
  • Cardiac sodium currents (I(Na)) exhibit significantly lower TTX sensitivity compared to neuronal or skeletal muscle channels.
  • The interaction of TTX with cardiac calcium currents (I(Ca)) has not been previously investigated.

Purpose of the Study:

  • To investigate the sensitivity of cardiac L-type calcium current (I(Ca)) to Tetrodotoxin (TTX).
  • To characterize the blocking kinetics and mechanism of TTX on cardiac I(Ca).
  • To compare the effects of TTX on cardiac I(Ca) and I(Na) using computational models.

Main Methods:

  • Conventional and action potential voltage clamp techniques were employed on isolated canine ventricular cells.
  • The effects of TTX on L-type calcium current were analyzed, including reversibility and inactivation kinetics.
  • Dose-response relationships were determined using the Hill equation, and nisoldipine was used to confirm the current as I(Ca).
  • Stick-and-ball models of Cav1.2 and Nav1.5 channels were constructed.

Main Results:

  • TTX reversibly blocked cardiac L-type calcium current (I(Ca)) with an IC(50) of 55 ± 2 μM and a Hill coefficient of 1.0 ± 0.04.
  • TTX did not alter the inactivation kinetics of I(Ca).
  • The TTX-sensitive current exhibited characteristics of I(Ca) under action potential voltage clamp, distinct from I(Na).

Conclusions:

  • This study provides the first evidence that Tetrodotoxin (TTX) interacts with and blocks cardiac L-type calcium current (I(Ca)).
  • The findings suggest distinct binding sites or mechanisms for TTX on cardiac calcium channels compared to sodium channels.
  • Computational modeling may help elucidate the structural basis for the differential effects of TTX on cardiac ion channels.

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