The calcium channel β2 (CACNB2) subunit repertoire in teleosts

Cloning of two zebrafish β2 subunit genes (β2.1 and β2.2) indicated they are membrane-associated guanylate kinase (MAGUK)-family genes. Zebrafish β2 genes show high conservation with mammals within the SH3 and guanylate kinase domains that comprise the "core" of MAGUK proteins, but β2.2 is much more divergent in sequence than β2.1. Alternative splicing occurs at the N-terminus and within the internal HOOK domain. In both β2 genes, alternative short ATG-containing first exons are separated by some of the largest introns in the genome, suggesting that individual transcript variants could be subject to independent cis-regulatory control. In the Tetraodon nigrovidis and Fugu rubripes genomes, we identified single β2 subunit gene loci. Comparative analysis of the teleost and human β2 loci indicates that the short 5' exon sequences are highly conserved. A subset of 5' exons appear to be unique to teleost genomes, while others are shared with mammals. Alternative splicing is temporally and spatially regulated in embryo and adult. Moreover, a different subset of spliced β2 transcript variants is detected in the embryonic heart compared to the adult.These studies refine our understanding of β2 subunit diversity arising from alternative splicing, and provide the groundwork for functional analysis of β2 subunit diversity in the embryonic heart.Voltage-dependent L-type Ca2+ channels (V-LTCC) are essential for the initiation and regulation of excitation-contraction coupling in cardiac muscle. In addition, Ca2+ entry through V-LTCC channels can also serve as a second messenger to modulate regulatory protein kinases, calmodulin and beta-adrenergic responses [3]. Genetic mutation of key Ca2+ homeostasis proteins is frequently associated with defects in both cardiac cell differentiation and contractility, suggesting Ca2+ signaling is essential for normal cardiac development [4-7]. Ca2+ signals can also contribute to the control of gene expression [8]. Ca2+ influx through V-LTCC can