Cortisol influences the ontogeny of both alpha- and beta-subunits of the cardiac sodium channel in fetal sheep.
During development, the heart has to adapt to changes in shape, size and, at birth, to significant changes in arterial pressure. The orderly contraction of the heart is dependent on the coordinated expression of ion channels at appropriate densities in individual cardiac myocytes. The present study demonstrated that the expression of the alpha-subunit of the cardiac sodium channel, SCN5a, was high at mid gestation but then decreased until 10 days before birth before increasing again. Whereas the beta-subunit, SCN1b, gradually increased in expression towards partum, there was no detectable expression of SCN3b at any gestational time point. Fetal adrenalectomy prior to the normal prepartum surge in cortisol caused a reduction in expression of SCN1b and a 7.0 kb transcript of SCN5a, but not the major 8.5 kb transcript. Conversely, cortisol infusion into immature fetuses precociously increased expression levels of SCN1b and the SCN5a 7.0 kb transcript. The results show that cortisol regulates cardiac SCN gene expression in fetal sheep during late gestation. These findings could have implications for the aetiology of sudden infant death syndrome and for the intrauterine programming of adult cardiovascular disease.
Fahmi
A I
AI
Department of Biochemistry, University of Cambridge, Downing Site, Cambridge CB2 1QW, UK.
Forhead
A J
AJ
Fowden
A L
AL
Vandenberg
J I
JI
D000315:Adrenalectomy; D000818:Animals; D005314:Embryonic and Fetal Development; D005865:Gestational Age; D006321:Heart / Q000187:drug effects / Q000196:embryology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology / Q000502:physiology*; D007231:Infant, Newborn; D009124:Muscle Proteins / Q000378:metabolism; D062554:NAV1.5 Voltage-Gated Sodium Channel; D020033:Protein Isoforms / Q000378:metabolism*; D012756:Sheep / Q000196:embryology*; D015222:Sodium Channels / Q000378:metabolism*; D013268:Stimulation, Chemical; D013398:Sudden Infant Death / Q000209:etiology
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D020033:Protein Isoforms; C568320:SCN5A protein, human; D015222:Sodium Channels; D006854:Hydrocortisone