Arrhythmogenic effect of a crude extract from sea anemone Condylactis gigantea: Possible involvement of rErg1 channels

• Published in: Toxicon (Oxford) 2013-06, Vol.67, p.47-54
• Main Authors: Santos, Yúlica, Martínez, Martín, Sandoval, Alejandro, Rodríguez, Armando A., Falcón, Andrés, Heimer de la Cotera, Edgar P., Aguilar, Manuel B., Flores, Pedro, Felix, Ricardo, Arreguín, Roberto
• Format: Article
• Language: English
• Subjects: Alterations; Animals; Anthozoa; cardiomyocytes; Channels; Chromatography; Cnidarian Venoms - pharmacology; Condylactis gigantea; Erg1; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels - drug effects; Ether-A-Go-Go Potassium Channels - metabolism; Ether-a-go-go-related gene; Heart; Heart - drug effects; HEK293 Cells - drug effects; HEK293 Cells - metabolism; Humans; Ion channels; Long QT Syndrome - chemically induced; Long QT Syndrome - physiopathology; Long QT syndrome type 2; Male; Marine; molecular weight; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - physiology; Patch-clamp; Patch-Clamp Techniques; Peptides; physiology; potassium channels; Purification; Rats; Rats, Wistar; Recombinant; Recombinant Proteins - metabolism; Sea anemone; Sea Anemones - chemistry; signal transduction; Tissue Extracts - pharmacology; Toxins
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2013.02.015

Sea anemones possess a number of peptide toxins that target ion channels which provide powerful tools to study the molecular basis of diverse signaling pathways. It is also acknowledged that currents through Erg1 K+ channels in cardiac myocytes are important for electrical stability of the heart and alterations in its activity has been linked to the onset of a potentially life-threatening heart condition named long QT syndrome type 2. Here, we report that a crude extract from sea anemone Condylactis gigantea significantly increases the QT interval and has arrhythmogenic effects in the rat heart. Furthermore, a bioassay-guided purification procedure allowed the isolation of a chromatographic fraction containing a major component with a molecular mass of 4478 Da from the crude extract, which causes a significant inhibition of whole-cell patch-clamp currents through recombinant Erg1 channels, responsible of the rapid delayed rectifying current crucial for electrical activity in the heart. Further studies could provide relevant information on the molecular mechanism of C. gigantea peptide toxins which represent promising tools in studying the physiology of diverse ion channels. ► Toxins from sea anemones are used for studying ion channel structure and function. ► An extract and a low-molecular weight fraction from Condylactis gigantea venom were studied. ► The extract caused a prolongation in the QT interval in the rat ECG. ► A ∼5 kDa fraction isolated from this extract affected rErg1 channel activity.