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Exploration of huma...
Exploration of human, rat, and rabbit embryonic cardiomyocytes suggests K-channel block as a common teratogenic mechanism
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- Danielsson, Christian (författare)
- Karolinska University Hospital, Sweden
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- Brask, Johan (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Skold, Anna-Carin (författare)
- AstraZeneca RandD Sodertalje, Sweden
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- Genead, Rami (författare)
- Karolinska University Hospital, Sweden
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- Andersson, Agneta (författare)
- Karolinska University Hospital, Sweden
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- Andersson, Ulf (författare)
- AstraZeneca RandD Sodertalje, Sweden
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- Stockling, Kenneth (författare)
- AstraZeneca RandD Sodertalje, Sweden
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- Pehrson, Rickard (författare)
- AstraZeneca RandD Sodertalje, Sweden
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- Grinnemo, Karl-Henrik (författare)
- Karolinska Institutet
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- Salari, Sajjad (författare)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet
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- Hellmold, Heike (författare)
- Karolinska Institutet
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- Danielsson, Bengt (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmanet Dev Grp, Sweden Uppsala University, Sweden
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- Sylven, Christer (författare)
- Karolinska Institutet
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- Elinder, Fredrik (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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(creator_code:org_t)
- 2012-09-20
- 2013
- Engelska.
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP): Policy B. - 0008-6363 .- 1755-3245. ; 97:1, s. 23-32
- Relaterad länk:
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Several drugs blocking the rapidly activating potassium (K-r) channel cause malformations (including cardiac defects) and embryonic death in animal teratology studies. In humans, these drugs have an established risk for acquired long-QT syndrome and arrhythmia. Recently, associations between cardiac defects and spontaneous abortions have been reported for drugs widely used in pregnancy (e.g. antidepressants), with long-QT syndrome risk. To investigate whether a common embryonic adverse-effect mechanism exists in the human, rat, and rabbit embryos, we made a comparative study of embryonic cardiomyocytes from all three species. less thanbrgreater than less thanbrgreater thanPatch-clamp and quantitative-mRNA measurements of K-r and slowly activating K (K-s) channels were performed on human, rat, and rabbit primary cardiomyocytes and cardiac samples from different embryo-foetal stages. The K-r channel was present when the heart started to beat in all species, but was, in contrast to human and rabbit, lost in rats in late organogenesis. The specific K-r-channel blocker E-4031 prolonged the action potential in a species- and development-dependent fashion, consistent with the observed K-r-channel expression pattern and reported sensitive periods of developmental toxicity. E-4031 also increased the QT interval and induced 2:1 atrio-ventricular block in multi-electrode array electrographic recordings of rat embryos. The K-s channel was expressed in human and rat throughout the embryo-foetal period but not in rabbit. less thanbrgreater than less thanbrgreater thanThis first comparison of mRNA expression, potassium currents, and action-potential characteristics, with and without a specific K-r-channel blocker in human, rat, and rabbit embryos provides evidence of K-r-channel inhibition as a common mechanism for embryonic malformations and death.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- Arrhythmia
- Embryo
- K-channel
- Long-QT syndrome
- Teratogenicity
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Danielsson, Chri ...
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Brask, Johan
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Skold, Anna-Cari ...
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Genead, Rami
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Andersson, Agnet ...
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Andersson, Ulf
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visa fler...
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Stockling, Kenne ...
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Pehrson, Rickard
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Grinnemo, Karl-H ...
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Salari, Sajjad
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Hellmold, Heike
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Danielsson, Beng ...
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Sylven, Christer
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Elinder, Fredrik
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinsk biotek ...
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och Medicinsk biotek ...
- Artiklar i publikationen
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Cardiovascular R ...
- Av lärosätet
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Linköpings universitet
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Uppsala universitet
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Karolinska Institutet