Developmental differences in myocardial transmembrane Na+ transport:

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Developmental differences in myocardial transmembrane Na+ transport:
Oshiyama, Natália Ferreira; Pereira, Ana Helena Macedo; Cardoso, Alisson Campos; Franchini, Kleber Gomes; Bassani, José Wilson Magalhães; Bassani, Rosana Almada, 2022, "Developmental differences in myocardial transmembrane Na+ transport:", https://doi.org/10.25824/redu/329KGJ, Repositório de Dados de Pesquisa da Unicamp , V1
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Description
Little is currently known about possible developmental changes in myocardial Na+ handling, which may have impact on cell excitability and Ca2+ content. Resting intracellular Na+ concentration ([Na+]i), measured in freshly isolated rat ventricular myocytes with CoroNa green, was not significantly different in neonates (3–5 days old) and adults, but electrical stimulation caused marked [Na+]i rise only in neonates. Inhibition of L-type Ca2+ current by CdCl2 abolished not only systolic Ca2+ transients, but also activity-dependent intracellular Na+ accumulation in immature cells. This indicates that the main Na+ influx pathway during activity is the Na+/Ca2+ exchanger, rather than voltage-dependent Na+ current (INa), which was not affected by CdCl2. In immature myocytes, INa density was two-fold greater, inactivation was faster, and the current peak occurred at less negative transmembrane potential (Em) than in adults. Na+ channel steady-state activation and inactivation curves in neonates showed a rightward shift, which should increase channel availability at diastolic Em, but also require greater depolarization for excitation, which was observed experimentally and reproduced in computer simulations. Ventricular mRNA levels of Nav1.1, Nav1.4 and Nav1.5 pore-forming isoforms were greater in neonate ventricles, while a decrease was seen for the β1 subunit. Both molecular and biophysical changes in the channel profile may contribute to the differences in INa density and voltage-dependence, and also to the less negative threshold Em, in neonates compared to adults. The apparently lower excitability in immature ventricle may confer protection against the development of spontaneous activity in this tissue. (2022-04-30)
Subject Engineering; Medicine, Health and Life Sciences
Keyword Postnatal development, Myocardium, Action potential, Voltage-dependent Na+ current, Na+/Ca2+ exchanger
Related Publication Oshiyama NF, Pereira AHM, Cardoso AC, Franchini KG, Bassani JWM, Bassani RA (2022) Developmental differences in myocardial transmembrane Na + transport: implications for excitability and Na + handling. J Physiol doi: 10.1113/JP282661
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