Valinomycin shortening of action potential of embryonic chick hearts.
The effects of valinomycin, an agent known to increase the K+ conductance (gK) of lipid bilayer membranes and to be an uncoupler of oxidative phosphorylation, were examined on young (3 days old) and old (15-19 days old) embryonic chick hearts. In the old hearts, valinomycin produced pronounced shortening of the action potential plateau, and often only the spike component remained. The rate of rise of the action potential was usually not affected (slightly diminished sometimes). Addition of dimethylsulfoxide (2 percent), the vehicle for the valinomycin, did not cause shortening of the plateau. The diminution of the plateau by valinomycin at 1 mug/ml was usually obtained after incubation for 1 h; larger doses produced prominent effects within 15 min. The threshold concentration was about 0.1 mug/ml. Cooling, isoproterenol, Ba++, Sr++, and tetraethylammonium partially relengthened the plateau shortened by valinomycin. Lowering of external K+ also lengthened the plateau slightly in the presence of valinomycin. Young embryonic hearts were more resistant to valinomycin, and it was necessary to incubate with 20-40 mug/ml for 1-2 h to produce a significant diminution in plateau. In both young and old hearts, the resting potential was not increased by valinomycin, even though young hearts have a low resting potential (similar to minus 40 mV) mainly because of a low gK. These results suggest that the kinetics of the changes in gK during the action potential plateau may be more greatly affected by valinomycin than the steady-state gK of the resting membrane. In addition to such a direct effect on the sarcolemma, valinomycin could also exert an indirect effect by blocking the slow inward current through ATP depletion.
D000200:Action Potentials / Q000187:drug effects*; D000367:Age Factors; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002642:Chick Embryo; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D013324:Strontium / Q000494:pharmacology; D013696:Temperature; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014634:Valinomycin / Q000494:pharmacology*
D013757:Tetraethylammonium Compounds; D014634:Valinomycin; D001464:Barium; D007545:Isoproterenol; D011188:Potassium; D004121:Dimethyl Sulfoxide; D013324:Strontium