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Effects of tetrodotoxin on heart cell aggregates. Phase resetting and annihilation of activity

A Shrier1, J R Clay, R M Brochu

  • 1Department of Physiology, McGill University, Montreal, Quebec, Canada.

Biophysical Journal
|September 1, 1990
PubMed

Insights

Low concentrations of tetrodotoxin (TTX) affect heart cell electrical activity by reducing action potential speed but not beat rate. TTX can even stop activity at higher concentrations, impacting cardiac electrophysiology.

Area of Science:

  • Cardiac Electrophysiology
  • Pharmacology
  • Biophysics

Background:

  • Spontaneous activity in embryonic chick atrial heart cells is crucial for cardiac development.
  • Tetrodotoxin (TTX) is a known blocker of voltage-gated sodium channels (INa).
  • Understanding TTX's effects on cardiac rhythm is vital for studying ion channel function.

Purpose of the Study:

  • To investigate the impact of low tetrodotoxin (TTX) concentrations on the phase resetting of embryonic chick atrial heart cell aggregates.
  • To analyze the effects of TTX on action potential characteristics and spontaneous activity.
  • To model the influence of TTX on INa channel block.

Main Methods:

  • Experimental application of brief duration current pulses to heart cell aggregates.
  • Measurement of maximal upstroke velocity (Vmax) and beat rate.
  • Theoretical modeling of electrical activity incorporating TTX's effect on INa channels.

Main Results:

  • TTX reduced Vmax in a concentration-dependent manner for concentrations below 10(-7) M.
  • Beat rate remained unaffected within this concentration range.
  • Activity annihilation was observed in some preparations at approximately 10(-7) M TTX.

Conclusions:

  • TTX at low concentrations primarily affects action potential upstroke velocity, not beat rate, in these cells.
  • The results support a model of tonic block of INa channels by TTX.
  • Cardiac electrophysiological responses to TTX are concentration-dependent and can lead to activity arrest.

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