Sea anemone toxin AdE-1 modifies both sodium and potassium currents of rat cardiomyocytes

AdE-1, a cardiotonic peptide recently isolated from the sea anemone Aiptasia diaphana, contains 44 amino acids with a molecular weight of 4907D. It was previously found to resemble other sea anemone type 1 and 2 Na+ channel toxins, enhancing contractions of rat cardiomyocytes and slowing their twitch relaxation. However, it did not induce spontaneous twitches. AdE-1 increased the duration of the cardiomyocyte action potential and decreased its amplitude and its time-to-peak in a concentration-dependent manner without affecting its threshold and cell resting potential. Nor did it generate the early and delayed after-depolarizations characteristic of sea anemone Na+ channel toxins. To further understand its mechanism of action we investigated the effect of AdE-1 on the major ion currents of rat cardiomyocytes. Here we show that AdE-1 markedly slowed inactivation of Na+ current, enhancing and prolonging the current influx with no effect on current activation, possibly through direct interaction with the site 3 receptor of the Na+ channel. No significant effect of AdE-1 on the Ca2+ current was observed but, unexpectedly, AdE-1 significantly increased the amplitude of the transient component of the K+ current, shifting the current threshold to more negative membrane potentials. This effect on the K+ current has not been found in any other sea anemone toxin and may explain the exclusive reduction in action potential amplitude and the...
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ ChemBio Source Type: research