The role of reduced potassium conductance in generating triggered activity in guinea-pig ventricular muscle.
This study investigates the role of reducing potassium conductance (gK) in generating delayed afterdepolarizations and triggered activity in small preparations of ventricular muscle from guinea-pig hearts. We used agents believed to reduce gK (low or absent K0, tetraethylammonium (TEA), CsCl) and we used ouabain (10(-6) M) to induce delayed afterdepolarizations. Treatment with ouabain only caused subthreshold delayed afterdepolarizations or occasionally non-sustained triggered activity. Exposure to Tyrode's solution with K reduced from 4 to 2 mM or K-free Tyrode's solution, with or without ouabain, caused subthreshold delayed afterdepolarizations and sometimes non-sustained triggered activity. Exposure to Tyrode's solution containing TEA and ouabain caused sustained triggered activity, supporting the hypothesis that accumulation of extracellular K inhibits the development of triggered activity. Presumably, the reduction in gK caused by TEA is not reversed by accumulation of extracellular K so that the delayed afterdepolarizations in the presence of persistently reduced gK are large enough to induce sustained triggered activity. Under extreme conditions, when Cs replaced K and half the NaCl was replaced by TEA, delayed afterdepolarizations occurred in the presence of markedly reduced gK, the result being the rapid development of sustained triggered activity, even at the basic drive rate of 1 Hz. Our results suggest that reduced gK plays an important role in the development of triggered activity.
Gilat
E
E
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.
Nordin
C W
CW
Aronson
R S
RS
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D004553:Electric Conductivity / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D010210:Papillary Muscles / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D011188:Potassium / Q000378:metabolism / Q000493:pharmacokinetics / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D016276:Ventricular Function
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D010042:Ouabain; D019789:Tetraethylammonium; D011188:Potassium