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Characterization of maturation of neuronal voltage-gated sodium channels SCN1A and SCN8A in rat myocardium.

Krause U, Alflen C, Steinmetz M, Müller MJ, Quentin T, Paul T - Mol Cell Pediatr (2015)

Bottom Line: SCN1A protein level decreased after birth in contrast to RNA expression.The high expression level of SCN1A in the perinatal period and early infancy indicates its importance in preserving a regular cardiac rhythm in this early phase of life.Altered regulation of sodium channels might result in severe cardiac rhythm disturbances.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Cardiology and Intensive Care Medicine, University Medical Center, Georg August University, Göttingen, Robert-Koch-Str. 40, 37099, Göttingen, Germany. ukrause1@gwdg.de.

ABSTRACT

Background: Sodium channels predominantly expressed in brain are expressed in myocardial tissue and play an important role in cardiac physiology. Alterations of sodium channels are known to result in neurological disease in infancy and childhood. It will be of interest to study the expression of brain-type sodium channels in the developing myocardium.

Methods: The expression of neuronal sodium channels (SCN1A, SCN8A) and the cardiac isoform SCN5A in the developing rat myocardium was studied by rtPCR, Western blot, and immunohistochemistry at different stages of antenatal and postnatal development.

Results: Significant changes of sodium channel expression during development were detected. Whereas SCN5A RNA increased to maximum levels on day 21 after birth, the highest SCN1A RNA levels were detected on day 1 to 7 after birth. SCN8A RNA was maximally expressed during embryonic development. At the protein level, the amount of SCN5A protein increased along with the RNA level. SCN1A protein level decreased after birth in contrast to RNA expression. Western blot could not detect SCN8A protein in the myocardium at any stage of development. Immunohistochemistry however proved the presence of SCN8A protein in the developing rat myocardium.

Conclusions: Heart- and brain-type sodium channels are differentially expressed during ontogenesis. The high expression level of SCN1A in the perinatal period and early infancy indicates its importance in preserving a regular cardiac rhythm in this early phase of life. Altered regulation of sodium channels might result in severe cardiac rhythm disturbances.

No MeSH data available.


Related in: MedlinePlus

SCN5A mRNA expression. Expression of SCN5A mRNA steadily increased after birth compared to the embryonic level of development. The slight drop of mRNA expression after day 21 was not significant. Significance refers to the amount of mRNA on day 17 of embryonic development (Abbreviations and levels of significance as depicted in Figure 1).
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Fig2: SCN5A mRNA expression. Expression of SCN5A mRNA steadily increased after birth compared to the embryonic level of development. The slight drop of mRNA expression after day 21 was not significant. Significance refers to the amount of mRNA on day 17 of embryonic development (Abbreviations and levels of significance as depicted in Figure 1).

Mentions: Analyzing mRNA the expression of SCN5A at different stages of ontogenesis, the amount of SCN5A mRNA significantly increased after birth to 201 ± 21% on day 1 (n = 5, p < 0.001), to 257 ± 30% on day 7 (n = 5, p < 0.001), and to 353 ± 25% on day 21 (n = 5, p < 0.001), respectively. This observation was similar to the results for SCN1A mRNA in this study. A slight and non-significant drop to 289 ± 16% was found at the age of 6 weeks. However, this amount of SCN5A mRNA was still significantly higher in comparison with the prenatal mRNA amount at stage E17 (n = 5, p < 0.001, Figure 2).Figure 2


Characterization of maturation of neuronal voltage-gated sodium channels SCN1A and SCN8A in rat myocardium.

Krause U, Alflen C, Steinmetz M, Müller MJ, Quentin T, Paul T - Mol Cell Pediatr (2015)

SCN5A mRNA expression. Expression of SCN5A mRNA steadily increased after birth compared to the embryonic level of development. The slight drop of mRNA expression after day 21 was not significant. Significance refers to the amount of mRNA on day 17 of embryonic development (Abbreviations and levels of significance as depicted in Figure 1).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4530575&req=5

Fig2: SCN5A mRNA expression. Expression of SCN5A mRNA steadily increased after birth compared to the embryonic level of development. The slight drop of mRNA expression after day 21 was not significant. Significance refers to the amount of mRNA on day 17 of embryonic development (Abbreviations and levels of significance as depicted in Figure 1).
Mentions: Analyzing mRNA the expression of SCN5A at different stages of ontogenesis, the amount of SCN5A mRNA significantly increased after birth to 201 ± 21% on day 1 (n = 5, p < 0.001), to 257 ± 30% on day 7 (n = 5, p < 0.001), and to 353 ± 25% on day 21 (n = 5, p < 0.001), respectively. This observation was similar to the results for SCN1A mRNA in this study. A slight and non-significant drop to 289 ± 16% was found at the age of 6 weeks. However, this amount of SCN5A mRNA was still significantly higher in comparison with the prenatal mRNA amount at stage E17 (n = 5, p < 0.001, Figure 2).Figure 2

Bottom Line: SCN1A protein level decreased after birth in contrast to RNA expression.The high expression level of SCN1A in the perinatal period and early infancy indicates its importance in preserving a regular cardiac rhythm in this early phase of life.Altered regulation of sodium channels might result in severe cardiac rhythm disturbances.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Cardiology and Intensive Care Medicine, University Medical Center, Georg August University, Göttingen, Robert-Koch-Str. 40, 37099, Göttingen, Germany. ukrause1@gwdg.de.

ABSTRACT

Background: Sodium channels predominantly expressed in brain are expressed in myocardial tissue and play an important role in cardiac physiology. Alterations of sodium channels are known to result in neurological disease in infancy and childhood. It will be of interest to study the expression of brain-type sodium channels in the developing myocardium.

Methods: The expression of neuronal sodium channels (SCN1A, SCN8A) and the cardiac isoform SCN5A in the developing rat myocardium was studied by rtPCR, Western blot, and immunohistochemistry at different stages of antenatal and postnatal development.

Results: Significant changes of sodium channel expression during development were detected. Whereas SCN5A RNA increased to maximum levels on day 21 after birth, the highest SCN1A RNA levels were detected on day 1 to 7 after birth. SCN8A RNA was maximally expressed during embryonic development. At the protein level, the amount of SCN5A protein increased along with the RNA level. SCN1A protein level decreased after birth in contrast to RNA expression. Western blot could not detect SCN8A protein in the myocardium at any stage of development. Immunohistochemistry however proved the presence of SCN8A protein in the developing rat myocardium.

Conclusions: Heart- and brain-type sodium channels are differentially expressed during ontogenesis. The high expression level of SCN1A in the perinatal period and early infancy indicates its importance in preserving a regular cardiac rhythm in this early phase of life. Altered regulation of sodium channels might result in severe cardiac rhythm disturbances.

No MeSH data available.


Related in: MedlinePlus