Effects of bimoclomol, the novel heat shock protein coinducer, in dog ventricular myocardium

Gyula Szigeti, Tamás Bányász, János Magyar, Ágnes Körtvély, Péter Szigligeti, László Kovács, Andrea Jednákovits, Péter P. Nánási

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Abstract

The effects of the novel HSP-coinducer bimoclomol was studied on action potentials, ionic currents and [Ca2+](i) transients in isolated canine ventricular myocytes using conventional microelectrode techniques and whole cell voltage clamp combined with fluorescent [Ca2+](i) measurements. Contractility was studied in right ventricular trabeculae. All preparations were paced with a frequency of 0.2 Hz. Bimoclomol (100 μM) shortened action potential duration measured at 50% repolarization, but lengthened action potentials at the 90% repolarization level, decreased action potential amplitude and maximum depolarization velocity in a reversible manner. In voltage clamped myocytes, the drug activated a steady-state outward current at positive membrane potentials leaving the peak inward current unaffected. [Ca2+](i) transients, measured under voltage clamp control, were increased in amplitude and had accelerated decay kinetics in the presence of the compound, in addition to reduction of diastolic [Ca2+](i). Bimoclomol significantly decreased the force of contraction in right ventricular trabeculae. Comparison of present data to previous results indicate that the cardiac effects of bimoclomol strongly depend on actual experimental conditions. The reduced contractility in spite of the increased amplitude of [Ca2+](i) transients suggests that 100 μM bimoclomol may decrease calcium sensitivity of the contractile apparatus. (C) 2000 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)73-79
Number of pages7
JournalLife Sciences
Volume67
Issue number1
DOIs
Publication statusPublished - May 26 2000

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Keywords

  • Bimoclomol
  • Dog
  • Heat shock protein coinducer
  • Ventricular myocardium

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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