K-OPENING PROPERTIES OF A NOVEL COMPOUND, NIP-121, IN GUINEA-PIG MYOCARDIUM AS COMPARED WITH THOSE OF CROMAKALIM( CHANNEL)

Myocardial effects of NIP-121, a novel compound with potent vasorelaxa nt activity, were examined in comparison with those of cromakalim in i solated tissue and cells from guinea pig hearts. NIP-121 and cromakali m concentration-dependently reduced the action potential duration (APD ) of isolated papillary muscle; the effect was antagonized by glibencl amide. In isolated ventricular tissue, NIP-121 and cromakalim decrease d the contractile force concentration dependently. In these two experi ments, the potency of NIP-121 was similar to 20 times higher than that of cromakalim. The effects of NIP-121 and cromakalim on membrane curr ents were examined in voltage-clamped ventricular myocytes. NIP-121 (1 0(-6)M) and cromakalim (3 x 10(-5)M) increased the steady-state outwar d currents. The normal inwardly rectifying current-voltage relationshi p changed to a linear relationship that reversed at the K+ current rev ersal potential. The current activated by NIP-121 and cromakalim was i nhibited either by glibenclamide or by increased intracellular ATP con centration. NIP-121, at this concentration, had little effect on the c alcium current. Thus, NIP-121 was demonstrated to produce AP shortenin g and decrease in contractile force through activation of ATP-sensitiv e K+ currents in cardiac muscle, with a potency similar to 20 times hi gher than that of cromakalim.