title: Arrhythmogenic effect of a crude extract from sea anemone Condylactis gigantea: possible involvement of rErg1 channels.
abstract: 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.
authors.affiliation: Departamento de Química de Biomacromoléculas, Instituto de Química, Universidad Nacional Autónoma de México (UNAM), Mexico.
authors.forename: Yúlica
authors.initials: Y
authors.lastname: Santos
authors.forename: Martín
authors.initials: M
authors.lastname: Martínez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sandoval
authors.forename: Armando A
authors.initials: AA
authors.lastname: Rodríguez
authors.forename: Andrés
authors.initials: A
authors.lastname: Falcón
authors.forename: Edgar P
authors.initials: EP
authors.lastname: Heimer de la Cotera
authors.forename: Manuel B
authors.initials: MB
authors.lastname: Aguilar
authors.forename: Pedro
authors.initials: P
authors.lastname: Flores
authors.forename: Ricardo
authors.initials: R
authors.lastname: Felix
authors.forename: Roberto
authors.initials: R
authors.lastname: Arreguín
mesh_terms: D000818:Animals; D003064:Cnidarian Venoms / Q000494:pharmacology*; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D057809:HEK293 Cells / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D012615:Sea Anemones / Q000737:chemistry*; D014020:Tissue Extracts / Q000494:pharmacology*
chemical_list: D003064:Cnidarian Venoms; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D011994:Recombinant Proteins; D014020:Tissue Extracts