Referenced in: none

Automatically associated channels: SK2 , SK3

Title: Ca(2+) -activated K(+) current is essential for maintaining excitability and gene transcription in early embryonic cardiomyocytes.

Authors: S Karppinen, R Rapila, N Naumenko, T Tuomainen, J T Koivumäki, S L Hänninen, T Korhonen, P Tavi

Journal, date & volume: Acta Physiol (Oxf), 2015 Jun 12 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26095188

Abstract
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.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.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.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.