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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

Analysis of SCN1A protein expression. In contrast to rtPCR results, Western blot analysis of SCN1A protein expression showed a progressive decline with postnatal development (upper panel). As a control, protein expression of GAPDH showed no changes with development (lower panel; abbreviations as depicted in Figure 1).
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Fig4: Analysis of SCN1A protein expression. In contrast to rtPCR results, Western blot analysis of SCN1A protein expression showed a progressive decline with postnatal development (upper panel). As a control, protein expression of GAPDH showed no changes with development (lower panel; abbreviations as depicted in Figure 1).

Mentions: In order to determine the levels of SCN1A, SCN5A, and SCN8A protein (Nav1.1, Nav1.5, and Nav1.6, respectively), Western blot analysis was performed from samples of rat myocardium at the same developmental stages as PCR analysis had been conducted. In contrast to distribution of mRNA expression of SCN1A throughout ontogenetic development, SCN1A protein levels were highest during the embryonic stage of development and initially decreased slightly at day 1 of life (91 ± 47%). On day 7, a further decrease of protein amount of SCN1A was observed (65 ± 43%). Both changes, however, did not reach statistical significance compared to developmental stage E17 (n = 3). After 21 days and 6 weeks of life, SCN1A protein amount dropped significantly to 56 ± 38% (ventricular myocardium, day 21), to 57 ± 39% (atrial myocardium, day 21, p < 0.05, n = 3, ventricular and atrial myocardium), to 51 ± 35% (ventricular myocardium 6 weeks, p < 0.01, n = 3), and to 43 ± 29% (atrial myocardium 6 weeks, p > 0.001, n = 3, Figures 1 and 4).Figure 4


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)

Analysis of SCN1A protein expression. In contrast to rtPCR results, Western blot analysis of SCN1A protein expression showed a progressive decline with postnatal development (upper panel). As a control, protein expression of GAPDH showed no changes with development (lower panel; abbreviations as depicted in Figure 1).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4530575&req=5

Fig4: Analysis of SCN1A protein expression. In contrast to rtPCR results, Western blot analysis of SCN1A protein expression showed a progressive decline with postnatal development (upper panel). As a control, protein expression of GAPDH showed no changes with development (lower panel; abbreviations as depicted in Figure 1).
Mentions: In order to determine the levels of SCN1A, SCN5A, and SCN8A protein (Nav1.1, Nav1.5, and Nav1.6, respectively), Western blot analysis was performed from samples of rat myocardium at the same developmental stages as PCR analysis had been conducted. In contrast to distribution of mRNA expression of SCN1A throughout ontogenetic development, SCN1A protein levels were highest during the embryonic stage of development and initially decreased slightly at day 1 of life (91 ± 47%). On day 7, a further decrease of protein amount of SCN1A was observed (65 ± 43%). Both changes, however, did not reach statistical significance compared to developmental stage E17 (n = 3). After 21 days and 6 weeks of life, SCN1A protein amount dropped significantly to 56 ± 38% (ventricular myocardium, day 21), to 57 ± 39% (atrial myocardium, day 21, p < 0.05, n = 3, ventricular and atrial myocardium), to 51 ± 35% (ventricular myocardium 6 weeks, p < 0.01, n = 3), and to 43 ± 29% (atrial myocardium 6 weeks, p > 0.001, n = 3, Figures 1 and 4).Figure 4

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