title: Ca(2+) -activated K(+) current is essential for maintaining excitability and gene transcription in early embryonic cardiomyocytes.
abstract: OBJECTIVE
  Activity of early embryonic cardiomyocytes relies on spontaneous Ca(2+) oscillations that are induced by interplay between sarcoplasmic reticulum (SR) - Ca(2+) release and ion currents of the plasma membrane. In a variety of cell types, Ca(2+) -activated K(+) current (IK(Ca) ) serves as a link between Ca(2+) signals and membrane voltage. This study aimed to determine the role of IK (Ca) in developing cardiomyocytes.
  
  
  METHODS
  Ion currents and membrane voltage of embryonic (E9-11) mouse cardiomyocytes were measured by patch clamp; [Ca(2+) ]i signals by confocal microscopy. Transcription of specific genes was measured with RT-qPCR and Ca(2+) -dependent transcriptional activity using NFAT-luciferase assay. Myocyte structure was assessed with antibody labelling and confocal microscopy.
  
  
  RESULTS
  E9-11 cardiomyocytes express small conductance (SK) channel subunits SK2 and SK3 and have a functional apamin-sensitive K(+) current, which is also sensitive to changes in cytosolic [Ca(2+) ]i . In spontaneously active cardiomyocytes, inhibition of IK (Ca) changed action and resting potentials, reduced SR Ca(2+) load and suppressed the amplitude and the frequency of spontaneously evoked Ca(2+) oscillations. Apamin caused dose-dependent suppression of NFAT-luciferase reporter activity, induced downregulation of a pattern of genes vital for cardiomyocyte development and triggered changes in the myocyte morphology.
  
  
  CONCLUSIONS
  The results show that apamin-sensitive IK (Ca) is required for maintaining excitability and activity of the developing cardiomyocytes as well as having a fundamental role in promoting Ca(2+) - dependent gene expression.
authors.affiliation: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Karppinen
authors.affiliation: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Rapila
authors.affiliation: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: N
authors.initials: N
authors.lastname: Naumenko
authors.affiliation: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Tuomainen
authors.affiliation: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: J T
authors.initials: JT
authors.lastname: Koivumäki
authors.affiliation: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.|Institute of Biomedicine, Department of Physiology and Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: S L
authors.initials: SL
authors.lastname: Hänninen
authors.affiliation: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Korhonen
authors.affiliation: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Tavi
mesh_terms: D000818:Animals; D001030:Apamin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D005260:Female; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D009130:Muscle, Smooth / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D011247:Pregnancy; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D001030:Apamin; D011188:Potassium; D002118:Calcium
keywords: Ca2+-oscillation; E-C-coupling; SK channels; calcineurin; development; heart