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Inward rectifier potassium current (IK1) and Kir2 composition of the zebrafish (Danio rerio) heart
Hassinen, M. Haverinen, J. Hardy, Matthew E. Sheils, H.A. Vornanen, M.
Hassinen, M.
Haverinen, J.
Hardy, Matthew E.
Sheils, H.A.
Vornanen, M.
Publication Date
2015-12
End of Embargo
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© 2015 Springer. Reproduced in accordance with the publisher's self-archiving policy.
The final publication is available at Springer via https://doi.org/10.1007/s00424-015-1710-8
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Abstract
Electrophysiological properties and molecular
background of the zebrafish (Danio rerio) cardiac inward rectifier
current (IK1) were examined. Ventricular myocytes of
zebrafish have a robust (−6.7±1.2 pA pF−1 at −120 mV)
strongly rectifying and Ba2+-sensitive (IC50=3.8 μM) IK1.
Transcripts of six Kir2 channels (drKir2.1a, drKir2.1b,
drKir2.2a, drKir2.2b, drKir2.3, and drKir2.4) were expressed
in the zebrafish heart. drKir2.4 and drKir2.2a were the dominant
isoforms in both the ventricle (92.9±1.5 and 6.3±1.5 %)
and the atrium (28.9±2.9 and 64.7±3.0 %). The remaining
four channels comprised together less than 1 and 7 % of the
total transcripts in ventricle and atrium, respectively. The four
main gene products (drKir2.1a, drKir2.2a, drKir2.2b,
drKir2.4) were cloned, sequenced, and expressed in HEK
cells for electrophysiological characterization. drKir2.1a was
the most weakly rectifying (passed more outward current) and
drKir2.2b the most strongly rectifying (passed less outward
current) channel, whilst drKir2.2a and drKir2.4 were intermediate
between the two. In regard to sensitivity to Ba2+ block,
drKir2.4 was the most sensitive (IC50=1.8 μM) and drKir2.1a
the least sensitive channel (IC50=132 μM). These findings
indicate that the Kir2 isoform composition of the zebrafish
heart markedly differs from that of mammalian hearts.
Furthermore orthologous Kir2 channels (Kir2.1 and Kir2.4)
of zebrafish and mammals show striking differences in Ba2+-
sensitivity. Structural and functional differences needs to be
taken into account when zebrafish is used as a model for
human cardiac electrophysiology, cardiac diseases, and in
screening cardioactive substances.
Version
Accepted manuscript
Citation
Hassinen M, Haverinen J, Hardy ME, Shiels HA and Vornanen M (2015) Inward rectifier potassium current (IK1) and Kir2 composition of the zebrafish (Danio rerio) heart. Pflugers Archiv – European Journal of Physiology. 467(12): 2437-2446.
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Article