Mechanical and electrophysiological effects of a hydroxyphenyl-substituted tetrahydroisoquinoline, SL-1, on isolated rat cardiac tissues

G. J. Chang, M. J. Su*, P. H. Lee, S. S. Lee, K. C.S. Liu

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

3 Scopus citations


The mechanisms of the positive inotropic action of a new synthetic tetrahydroisoquinoline compound, SL-1, were investigated in isolated rat cardiac tissues and ventricular myocytes. SL-1 produced a rapidly developing, concentration-dependent positive inotropic response in both atrial and ventricular muscles and a negative chronotropic effect in spontaneously beating right atria. The positive inotropic effect was not prevented by pretreatment with reserpine (3 mg/kg) or the α-adrenoceptor antagonist prazosin (1 μM), but was suppressed by either the β-adrenoceptor antagonist atenolol (3 μM) or the K+ channel blocker 4-aminopyridine (4AP, 1 mM). In the whole-cell recording study, SL-1 increased the plateau level and prolonged the action potential duration in a concentration-dependent manner and decreased the maximum upstroke velocity (V̇(max)) and amplitude of the action potential in isolated rat ventricular myocytes stimulated at 1.0 Hz. On the other hand, SL-1 had little effect on the resting membrane potential, although it caused a slight decrease at higher concentrations. Voltage clamp experiments revealed that the increase of action potential plateau and prolongation of action potential duration were associated with an increase of Ca2+ inward current (I(Ca)) via the activation of β-adrenoceptors and a prominent inhibition of 4AP-sensitive transient outward K+ current (I(to)) with an IC50 of 3.9 μM. Currents through the inward rectifier K+ channel (I(K1)) were also reduced. The inhibition of I(to) is characterized by a reduction in peak amplitude and a marked acceleration of current decay but without changes on the voltage dependence of steady-state inactivation. In addition to the inhibition of K+ currents, SL-1 also inhibited the Na+ inward current (I(Na)) with an IC50 of 5.4 μM, which was correlated with the decrease of V̇(max). We conclude that the positive inotropic effect of SL-1 may be due to an increase in Ca2+ current mediated via partial activation of β-adrenoceptors and an inhibition of K+ outward currents and the subsequent prolongation of action potentials.

Original languageEnglish
Pages (from-to)1651-1660
Number of pages10
JournalCanadian Journal of Physiology and Pharmacology
Issue number11
StatePublished - 1995
Externally publishedYes


  • Action potential
  • Inotropic and chronotropic action
  • Na, Ca and K currents
  • SL-1
  • Tetrahydroisoquinoline


Dive into the research topics of 'Mechanical and electrophysiological effects of a hydroxyphenyl-substituted tetrahydroisoquinoline, SL-1, on isolated rat cardiac tissues'. Together they form a unique fingerprint.

Cite this