Modulation of cardiac Na+ current phenotype by beta1-subunit expression

Area of Science:

• Cardiovascular physiology
• Molecular biology
• Ion channel research

Background:

• Neonatal rat cardiac sodium current (INa) differs significantly from adult INa, exhibiting slower activation/inactivation and altered voltage dependence.
• Similar developmental changes in INa are observed in cultured mouse atrial tumor (AT-1) cells.
• These developmental shifts resemble those seen in skeletal muscle Na+ channels, where beta1 subunit coexpression promotes maturation.

Purpose of the Study:

• To investigate the role of the beta1 subunit in the developmental maturation of cardiac INa.
• To test the hypothesis that beta1 subunit suppression prevents the development of a mature INa phenotype.

Main Methods:

• Cloning of the mouse beta1 subunit from AT-1 cell cDNA.
• Treatment of AT-1 cells with anti-beta1 antisense oligonucleotides.
• Recording of INa and delayed rectifier K+ current in cultured AT-1 cells.
• Comparison of INa properties between treated and untreated cells.

Main Results:

• The mouse beta1 subunit shares high amino acid identity with the rat beta1 subunit.
• AT-1 cells treated with anti-beta1 antisense oligonucleotides showed an immature INa at day 8 in culture.
• Untreated cells and cells treated with sense oligonucleotides exhibited a mature INa.
• The rapidly activating delayed rectifier K+ current was unaffected by the oligonucleotides.

Conclusions:

• Beta1 subunit expression is essential for the maturation of cardiac INa in AT-1 cells.
• Coexpression of alpha and beta1 subunits is required for achieving a mature cardiac INa phenotype.
• This study elucidates a key molecular mechanism underlying cardiac INa development.