Differential plasma membrane targeting of voltage‐dependent calcium channel subunits expressed in a polarized epithelial cell line

1 Voltage‐dependent calcium channels (VDCCs) show a highly non‐uniform distribution in many cell types, including neurons and other polarized secretory cells. We have examined whether this can be mimicked in a polarized epithelial cell line (Madin‐Darby canine kidney), which has been used extensively to study the targeting of proteins. 2 We expressed the VDCC α1A, α1B or α1C subunits either alone or in combination with accessory subunits α2‐δ and the different β subunits, and examined their localization immunocytochemically. An α1 subunit was only targeted to the plasma membrane if co‐expressed with the accessory subunits. 3 The combination α1C/α2‐δ and all β subunits was always localized predominantly to the basolateral membrane. It has been suggested that this is equivalent to somatodendritic targeting in neurons. 4 In contrast, the α1B subunit was expressed at the apical membrane with all the accessory subunit combinations, by 24 h after microinjection. This membrane destination shows some parallels with axonal targeting in neurons. 5 The α1A subunit was consistently observed at the apical membrane in the combinations α1A/α2‐δ/β1b or β4. In contrast, when co‐expressed with α2‐δ/β2a, α1A was clearly targeted to the basolateral membrane. 6 In conclusion, the VDCC α1 subunit appears to be the primary determinant for targeting the VDCC complex, but the β subunit can modify this destination, particularly for α1A.