Changes in membrane potentials and currents of ventricular cells of the guinea pig heart by a new cardiotonic drug, MCI-154.
Effects of MCI-154, a newly synthesized cardiotonic drug with vasodilator property, on the membrane potential and currents of the isolated papillary muscles and the single ventricular cells of the guinea pig were examined. MCI-154 (10(-7)-10(-4) M) increased the developed tension in a dose-dependent manner without significant changes in the action potential configuration of the guinea pig papillary muscle. The slow response action potential obtained by increasing the extracellular K+ concentration to 24 mM was augmented by MCI-154 (10(-6) and 10(-4) M). This effect of MCI-154 was not blocked by atenolol (10(-6) M). In voltage clamp experiments on single ventricular cells, the slow inward current was not affected, but the inward rectifier K+ current was reduced by higher concentration of MCI-154 (10(-4) M). Considering the "run down" phenomenon of the slow inward current, the possibility that MCI-154 might have a slight increasing effect on the slow inward current could not be ruled out. From these results, it can be concluded that the positive inotropic action of MCI-154 can be explained partially by the decrease in the inward rectifier K+ current, and probably by the increase in the Ca2+ sensitivity of the contractile protein system.
Katayama
S
S
Research Center, Mitsubishi Chemical Industries Limited, Yokohama, Japan.
Narimatsu
A
A
Suzuki
R
R
Iijima
T
T
Taira
N
N
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D010210:Papillary Muscles / Q000187:drug effects; D011724:Pyridazines / Q000494:pharmacology*
D002316:Cardiotonic Agents; D011724:Pyridazines; C052228:MCI 154