title: The chemical compound PTC124 does not affect cellular electrophysiology of cardiac ventricular myocytes.
abstract: OBJECTIVE
  Nonsense mutations that create premature termination codons (PTC) leading to disease by a mechanism of haploinsufficiency are relatively common in the SCN5A gene encoding the major sodium channel in heart. PTCs in SCN5A are associated with isolated conduction disease and Brugada syndrome (BrS). Pharmacological therapy does not exist for these disorders, but would be highly beneficial. Recently, an orally bio-available drug capable of suppressing premature termination, PTC124, has been identified that selectively induces ribosomal read-through of premature but not normal termination codons. In this study, we tested the acute and long-term effects of PTC124 on action potential characteristics of rabbit ventricular cardiomyocytes.
  
  
  METHODS
  The effects of PTC124 on action potentials of isolated adult rabbit ventricular cardiomyocytes were studied using the perforated patch-clamp methodology. Acute effects of PTC124 were measured in freshly isolated cardiomyocytes, while long term effects were measured after 48 h in cultured cardiomyocytes.
  
  
  RESULTS
  Resting membrane potential, maximum upstroke velocity, action potential amplitude and action potential duration at 20, 50 and 90% of repolarization were not affected by application of PTC124, neither acute nor after 48 h.
  
  
  CONCLUSIONS
  PTC124 has no acute or long-term effects on rabbit ventricular action potentials. These experiments form the basis for future studies evaluating the use of this therapy in preventing potentially lethal arrhythmias in patients with BrS and/or conduction disease.
authors: Heart Failure Research Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. T.T.Koopmann@amc.uva.nl
authors: Tamara T
authors: TT
authors: Koopmann
authors: Arie O
authors: AO
authors: Verkerk
authors: Connie R
authors: CR
authors: Bezzina
authors: Jacques M T
authors: JM
authors: de Bakker
authors: Arthur A M
authors: AA
authors: Wilde
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D006352:Heart Ventricles; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D010069:Oxadiazoles / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D000889:Anti-Arrhythmia Agents; D010069:Oxadiazoles; C515878:ataluren