The effect on rat embryonic heart rate of Na+-, K+ and Ca2+ channel blockers, and the human teratogen phenytoin, changes with gestational age
2013 (English)In: Birth defects research. Part B. Developmental and reproductice toxicology, ISSN 1542-9733, E-ISSN 1542-9741, Vol. 98, no 5, 416-427 p.Article in journal (Refereed) Published
To determine the changes in dependence on ion channels during rat cardiac development we compared the effects of four ion channel blockers on rat embryonic heart function during the organogenic period from gestational day (GD) 10-15. Rat embryos in culture were exposed to either the hERG potassium channel blocker dofetilide (400 nM), the sodium channel blocker lidocaine (250 μM) the L-type calcium channel blocker nifedipine (1.8 μM), or the multi-channel blocker phenytoin (200 μM). Lidocaine slowed the heart rate (HR) with the effect becoming more severe with increasing GD. Dofetilide slowed the embryonic HR and caused arrhythmias with the most severe effect on GD 11-13. Nifedipine primarily caused a negative inotropic effect except on GD 10 when it stopped the heart in most embryos. Phenytoin stopped the heart of most GD 10-12 embryos while on GD 13-15 phenytoin it slowed the heart. The results demonstrate that as the rat heart develops during the organogenic period its functional dependence on ion channels changes markedly. These changes are important for understanding drug effects on the embryo during pregnancy and the methodology used provides a simple procedure for assessing drug effects on the developing heart.
Place, publisher, year, edition, pages
2013. Vol. 98, no 5, 416-427 p.
Pharmacology and Toxicology
Research subject Behavioural Neuroscience; Toxicology
IdentifiersURN: urn:nbn:se:uu:diva-206881DOI: 10.1002/bdrb.21084ISI: 000328470100005OAI: oai:DiVA.org:uu-206881DiVA: diva2:645862