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Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
10:53

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents

Published on: July 3, 2013

Block and modified gating of cardiac calcium channel currents by terodiline

T Ogura1, S Jones, L M Shuba

  • 1Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7.

British Journal of Pharmacology
|September 14, 1999
PubMed

Insights

Terodiline, used for urinary incontinence, significantly blocks cardiac calcium channels (ICa,L), especially at higher concentrations and with increased heart rate. This explains its cardiac side effects and potential cardiotoxicity.

Area of Science:

  • Pharmacology
  • Cardiovascular Physiology
  • Ion Channel Electrophysiology

Background:

  • Terodiline is an anticholinergic/antispasmodic drug for urinary incontinence.
  • Adverse cardiac effects have restricted its clinical use.
  • Its impact on cardiac L-type calcium channels (ICa,L) requires detailed characterization.

Purpose of the Study:

  • To investigate the effects of terodiline on cardiac L-type calcium channel currents (ICa,L and IBa,L).
  • To determine the concentration-dependent block and kinetics of terodiline on these channels.
  • To relate these findings to the drug's therapeutic and cardiotoxic properties.

Main Methods:

  • Whole-cell patch-clamp electrophysiology was performed on guinea-pig ventricular myocytes.
  • Terodiline was applied at concentrations from 0.1 to 100 microM.
  • Currents carried by Ca2+ (ICa,L) and Ba2+ (IBa,L) were measured under varying conditions.

Main Results:

  • Terodiline inhibited ICa,L in a concentration-dependent manner, with an IC50 of 12.2-15.2 microM.
  • The block was use-dependent, increasing with higher pulsing rates and lower holding potentials.
  • Terodiline accelerated ICa,L decay and slowed channel recovery from inactivation, and also affected IBa,L.

Conclusions:

  • Terodiline exhibits significant use-dependent block of cardiac L-type calcium channels.
  • These electrophysiological effects provide a mechanistic basis for the drug's observed cardiotoxicity.
  • Understanding these channel interactions is crucial for evaluating terodiline's therapeutic index.

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