Distribution and relative expression levels of calcium channel β subunits within the chambers of the rat heart

Calcium channel β subunits expressed in rat atria and atrial myocytes are identified and their expression quantified and compared to β subunit expression in the ventricle. mRNAs encoding all four know β subunits are expressed in atrial myocytes including the following splice variants: β1a, β2b, β2c, β2e and β4d. The specific β2 splice variants expressed in the atria (β2b, β2c, β2e) differ from those previously reported from rat ventricle. β2 isoform is the most abundant β mRNA expressed in the heart and the amount of both β2 subunit mRNA and β2 subunit protein is significantly greater in the ventricles than in the atria. The expression of individual β2 splice variants varies with age and within different chambers of the heart. The β2b splice variant appears in both atria and ventricle in both young (4.5 week) and old (16 week) animals, the β2c isoform is more highly expressed in young as compared to old animals and the β2e splice variant is robustly expressed only in 4.5 week ventricle. β4 mRNA expression is higher in atrial tissue than in ventricles and its expression decreases in older animals. In contrast, the abundance of the β3 mRNA does not significantly change as a function of postnatal age. Antisense oligonucleotides targeting sequence common to all the β isoforms as well as that specific for β2 significantly reduced HVA calcium current density in isolated atrial cells confirming that the β2 subunits contribute to the regulation of HVA calcium current expression in the rat atria. The complexity of β isoform expression within the heart may provide a mechanism for functional fine-tuning of the cardiac HVA current.