MECHANICAL AND ELECTROPHYSIOLOGICAL STUDIES ON THE POSITIVE INOTROPICEFFECT OF 2-PHENYL-4-OXO-HYDROQUINOLINE IN RAT CARDIAC TISSUES

1 The pharmacological and electrophysiological effect of 2-phenyl-4-ox o-hydroquinoline (YT-1), a new synthetic agent, were determined in rat isolated cardiac tissues and ventricular myocytes. 2 YT-1 was found t o have a positive inotropic effect in both atria and ventricular muscl es but did not cause significant increases in the spontaneously beatin g rate of right atria. 3 The positive inotropic effect of YT-1 was ant agonized neither by beta-nor by alpha-adrenoceptor antagonists but was partially antagonized by a Ca2+ channel blocker (verapamil) and a Kchannel blocker (4-AP). 4 The action potential duration and amplitude of ventricular cells were progressively increased as the concentration of YT-1 was increased from 3 to 30 mum.5 A voltage clamp study reveal ed that the prolongation of action potential duration by YT-1 was asso ciated with a prominent inhibition of 4-AP-sensitive transient outward current (I(to)). At potentials negative to the reversal potential of Kl-channels, the inward current through these channels was partially r educed by YT-1. At potentials positive to the reversal potential, the outward current through these channels was affected very little. 6 Alt hough YT-1 blocked the amplitude of I(to), the voltage-dependence of t he steady-state inactivation of I(to), was unaffected. 7 Apart from th e inhibition of K+ currents, YT-1 also inhibited the sodium inward cur rent. 8 The evidence suggests that YT-1 increases the slow inward Ca2 current (I(Ca)) significantly. 9 It is concluded that the positive in otropic effect of YT-1 is due predominantly to the increase of I(Ca) a nd inhibition of I(to).