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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

SCN1A mRNA expression. Expression of SCN1A mRNA increased dramatically after birth and declined significantly with postnatal development. At the age 21 days and 6 weeks, respectively, mRNA expression in the ventricular myocardium exceeded atrial expression significantly (*p < 0.05; **p < 0.01; #p < 0.001). E17, embryonic day 17 after gestation; P1, 1st postnatal day; P7, 7th postnatal day, P21v., 21st postnatal day, ventricular myocardium; P21a., 21st postnatal day, atrial myocardium; W6v., 6th postnatal week, ventricular myocardium; W6a., 6th postnatal week, atrial myocardium; P, protein level; R, mRNA level.
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Fig1: SCN1A mRNA expression. Expression of SCN1A mRNA increased dramatically after birth and declined significantly with postnatal development. At the age 21 days and 6 weeks, respectively, mRNA expression in the ventricular myocardium exceeded atrial expression significantly (*p < 0.05; **p < 0.01; #p < 0.001). E17, embryonic day 17 after gestation; P1, 1st postnatal day; P7, 7th postnatal day, P21v., 21st postnatal day, ventricular myocardium; P21a., 21st postnatal day, atrial myocardium; W6v., 6th postnatal week, ventricular myocardium; W6a., 6th postnatal week, atrial myocardium; P, protein level; R, mRNA level.

Mentions: Analysis of mRNA expression of VGSC in the developing rat myocardium revealed differential expression of SCN1A, SCN5A, and SCN8A. A more than sixfold increase of SCN1A mRNA expression was found immediately after birth (645 ± 13%, n = 5, p < 0.001). As describes above, RNA expression at stage E17 was set to 100% as a reference value for all genes analyzed at any developmental stage. Whereas there was no significant change in the amount of SCN1A mRNA until day 7 of life (602 ± 22%, n = 5), a significant drop of mRNA levels was observed on day 21 (241 ± 14%, n = 5, p < 0.001, ventricular myocardium; 167 ± 32%, n = 5, p < 0.05, atrial myocardium, respectively) and at the age of 6 weeks (356 ± 40%, n = 5, p < 0.001, ventricular myocardium; 169 ± 43%, n = 5, p < 0.05, atrial myocardium, respectively). Compared to prenatal mRNA levels, however, SCNA1 expression was still 1.5 to 3 times higher on day 21 and 6 weeks after birth (Figure 1).Figure 1


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)

SCN1A mRNA expression. Expression of SCN1A mRNA increased dramatically after birth and declined significantly with postnatal development. At the age 21 days and 6 weeks, respectively, mRNA expression in the ventricular myocardium exceeded atrial expression significantly (*p < 0.05; **p < 0.01; #p < 0.001). E17, embryonic day 17 after gestation; P1, 1st postnatal day; P7, 7th postnatal day, P21v., 21st postnatal day, ventricular myocardium; P21a., 21st postnatal day, atrial myocardium; W6v., 6th postnatal week, ventricular myocardium; W6a., 6th postnatal week, atrial myocardium; P, protein level; R, mRNA level.
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Fig1: SCN1A mRNA expression. Expression of SCN1A mRNA increased dramatically after birth and declined significantly with postnatal development. At the age 21 days and 6 weeks, respectively, mRNA expression in the ventricular myocardium exceeded atrial expression significantly (*p < 0.05; **p < 0.01; #p < 0.001). E17, embryonic day 17 after gestation; P1, 1st postnatal day; P7, 7th postnatal day, P21v., 21st postnatal day, ventricular myocardium; P21a., 21st postnatal day, atrial myocardium; W6v., 6th postnatal week, ventricular myocardium; W6a., 6th postnatal week, atrial myocardium; P, protein level; R, mRNA level.
Mentions: Analysis of mRNA expression of VGSC in the developing rat myocardium revealed differential expression of SCN1A, SCN5A, and SCN8A. A more than sixfold increase of SCN1A mRNA expression was found immediately after birth (645 ± 13%, n = 5, p < 0.001). As describes above, RNA expression at stage E17 was set to 100% as a reference value for all genes analyzed at any developmental stage. Whereas there was no significant change in the amount of SCN1A mRNA until day 7 of life (602 ± 22%, n = 5), a significant drop of mRNA levels was observed on day 21 (241 ± 14%, n = 5, p < 0.001, ventricular myocardium; 167 ± 32%, n = 5, p < 0.05, atrial myocardium, respectively) and at the age of 6 weeks (356 ± 40%, n = 5, p < 0.001, ventricular myocardium; 169 ± 43%, n = 5, p < 0.05, atrial myocardium, respectively). Compared to prenatal mRNA levels, however, SCNA1 expression was still 1.5 to 3 times higher on day 21 and 6 weeks after birth (Figure 1).Figure 1

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