Cloning, Localization, and Functional Expression of Sodium Channel β1A Subunits

• Published in: The Journal of biological chemistry Vol. 275; no. 2; pp. 1079 - 1088
• Main Authors: Kazen-Gillespie, Kristin A., Ragsdale, David S., D'Andrea, Michael R., Mattei, Laura N., Rogers, Kathryn E., Isom, Lori L.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 14.01.2000
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.275.2.1079

Auxiliary β1 subunits of voltage-gated sodium channels have been shown to be cell adhesion molecules of the Ig superfamily. Co-expression of α and β1 subunits modulates channel gating as well as plasma membrane expression levels. We have cloned, sequenced, and expressed a splice variant of β1, termed β1A, that results from an apparent intron retention event. β1 and β1A are structurally homologous proteins with type I membrane topology; however, they contain little to no amino acid homology beyond the shared Ig loop region. β1A mRNA expression is developmentally regulated in rat brain such that it is complementary to β1. β1A mRNA is expressed during embryonic development, and then its expression becomes undetectable after birth, concomitant with the onset of β1 expression. In contrast, β1A mRNA is expressed in adult adrenal gland and heart. Western blot analysis revealed β1A protein expression in heart, skeletal muscle, and adrenal gland but not in adult brain or spinal cord. Immunocytochemical analysis of β1A expression revealed selective expression in brain and spinal cord neurons, with high expression in heart and all dorsal root ganglia neurons. Co-expression of αIIA and β1A subunits in Chinese hamster lung 1610 cells results in a 2.5-fold increase in sodium current density compared with cells expressing αIIA alone. This increase in current density reflected two effects of β1A: 1) an increase in the proportion of cells expressing detectable sodium currents and 2) an increase in the level of functional sodium channels in expressing cells. [3H]Saxitoxin binding analysis revealed a 4-fold increase in Bmax with no change inKD in cells coexpressing αIIA and β1A compared with cells expressing αIIA alone. β1A-expressing cell lines also revealed subtle differences in sodium channel activation and inactivation. These effects of β1A subunits on sodium channel function may be physiologically important events in the development of excitable cells.