The toxic effects on cardiac myocytes of tyledoside F, a cumulative neurotoxic cardiac glycoside isolated from Tylecodon grandiflorus

Abstract

To investigate the cardiac cellular effects of tyledoside F, a cumulative neurotoxic bufadienolide and ouabain, a non-cumulative cardenolide, the whole-cell clamp method was used to measure the Na-K pump current after the Na-K pump had been activated by high intracellular Na²⁺. The toxic effects of tyledoside F and ouabain on cardiac myocytes were also investigated by observing the effect of the Ca²⁺ overload on the viability of myocytes during a period of 75 min. From the results it is clear that there are similarities in the direct effects of tyledoside F and ouabain on the Na-K pump. It was found that ouabain inhibited the Na-K pump current more than that of tyledoside F. With regard to Ca²⁺ overload, there are differences in their mode of production of Ca²⁺ overload because cinnarizine protects the myocytes against ouabain-induced Ca²⁺ overload but not against tyledoside-induced Ca²⁺ overload. This study shows that with the whole-cell clamp technique tyledoside F inhibited the Na-K pump in a manner similar to inhibition of the pump by ouabain. Viability studies with myocytes indicated that tyledoside F also has other effects which are different from these of ouabain.