The role of reduced potassium conductance in generating triggered activity in guinea-pig ventricular muscle

This study investigates the role of reducing potassium conductance (g_K) in generating delayed afterdepolarizations and triggered activity in small preparations of ventricular muscle from guinea-pig hearts. We used agents believed to reduce g_K (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 g_K caused by TEA is not reversed by accumulation of extracellular K so that the delayed afterdepolarizations in the presence of persistently reduced g_K are large enough to induced 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 g_K, the result being the rapid development of sustained triggered activity, even at the basic drive rate of 1 Hz. Our results suggest that reduced g_K plays an important role in the development of triggered activity.