Effects of bimoclomol, the novel heat shock protein coinducer, in dog ventricular myocardium.
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 microM) 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 microM bimoclomol may decrease calcium sensitivity of the contractile apparatus.
Szigeti
G
G
Department of Physiology, University Medical School of Debrecen, Hungary.
Bányász
T
T
Magyar
J
J
Körtvély
A
A
Szigligeti
P
P
Kovács
L
L
Jednákovits
A
A
Nánási
P P
PP
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D004285:Dogs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D007094:Imides / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000166:cytology*; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology*; D016276:Ventricular Function
D015220:Calcium Channels; D006360:Heat-Shock Proteins; D007094:Imides; D011725:Pyridines; C108730:bimoclomol