Ca2+-activated adenylyl cyclase 1 introduces Ca2+-dependence to beta-adrenergic stimulation of HCN2 current

► HCN2 was co-expressed with Adenylyl Cylase 1 (AC1) or 6 (AC6) in cardiac myocytes. ► AC1 but not AC6 increased [cAMP]i, accelerated beating rate and shifted HCN2 positive. ► In both AC1 and AC6 groups, isoproterenol shifted HCN2 activation relation positive. ► BAPTA prevented the isoproterenol effect in the AC1 but not AC6 group. ► AC1 plays a key role in sensitivity of β-adrenergic stimulation of HCN to [Ca]i.