title: The sea anemone toxin AdE-1 modifies both sodium and potassium currents of rat cardiomyocytes.
abstract: AdE-1, a cardiotonic peptide recently isolated from the sea anemone Aiptasia diaphana, contains 44 amino acids and has a molecular mass of 4907 Da. 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. In the present study we show that AdE-1 markedly slowed inactivation of the 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 absence of the action potential disorders found with other toxins, such as early and delayed after-depolarizations.
authors.forename: Nir
authors.initials: N
authors.lastname: Nesher
authors.affiliation: *Department of Cell and Animal Biology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Eliahu
authors.initials: E
authors.lastname: Zlotkin
authors.forename: Binyamin
authors.initials: B
authors.lastname: Hochner
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D008297:Male; D008387:Marine Toxins / Q000302:isolation & purification / Q000633:toxicity*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology*; D015221:Potassium Channels; D051381:Rats; D017207:Rats, Sprague-Dawley; D012615:Sea Anemones / Q000737:chemistry*; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D008387:Marine Toxins; D015221:Potassium Channels; D015222:Sodium Channels