Mechanical and electrophysiological studies on the positive inotropic effect of 2‐phenyl‐4‐oxo‐hydroquinoline in rat cardiac tissues

The pharmacological and electrophysiological effect of 2‐phenyl‐4‐oxo‐hydroquinoline (YT‐1), a new synthetic agent, were determined in rat isolated cardiac tissues and ventricular myocytes. YT‐1 was found to have a positive inotropic effect in both atria and ventricular muscles but did not cause significant increases in the spontaneously beating rate of right atria. The positive inotropic effect of YT‐1 was antagonized neither by β‐nor by α‐adrenoceptor antagonists but was partially antagonized by a Ca²⁺ channel blocker (verapamil) and a K⁺ channel blocker (4‐AP). The action potential duration and amplitude of ventricular cells were progressively increased as the concentration of YT‐1 was increased from 3 to 30 μm. A voltage clamp study revealed that the prolongation of action potential duration by YT‐1 was associated with a prominent inhibition of 4‐AP‐sensitive transient outward current (I_to). At potentials negative to the reversal potential of K₁‐channels, the inward current through these channels was partially reduced by YT‐1. At potentials positive to the reversal potential, the outward current through these channels was affected very little. Although YT‐1 blocked the amplitude of I_to, the voltage‐dependence of the steady‐state inactivation of I_to, was unaffected. Apart from the inhibition of K⁺ currents, YT‐1 also inhibited the sodium inward current. The evidence suggests that YT‐1 increases the slow inward Ca²⁺ current (I_Ca) significantly. It is concluded that the positive inotropic effect of YT‐1 is due predominantly to the increase of I_Ca and inhibition of I_to. 1993 British Pharmacological Society