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

The effects of the novel HSP-coinducer bimoclomol was studied on action pot entials, ionic currents and [Ca2+](i) transients in isolated canine ventric ular myocytes using conventional microelectrode techniques and whole cell v oltage clamp combined with fluorescent [Ca2+](i) measurements. Contractilit y was studied in right ventricular trabeculae, All preparations were paced with a frequency of 0.2 Hz. Bimoclomol (100 mu M) shortened action potentia l 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 mem brane potentials leaving the peak inward current unaffected, [Ca2+](i) tran sients, measured under voltage clamp control, were increased in amplitude a nd had accelerated decay kinetics in the presence of the compound, in addit ion to reduction of diastolic [Ca2+](i). Bimoclomol significantly decreased the force of contraction in right ventricular trabeculae. Comparison of pr esent data to previous results indicate that the cardiac effects of bimoclo mol strongly depend on actual experimental conditions. The reduced contract ility in spite of the increased amplitude of [Ca2+](i) transients suggests that 100 mu M bimoclomol may decrease calcium sensitivity of the contractil e apparatus. (C) 2000 Elsevier Science Inc. All rights reserved.