The GK domain of the voltage-dependent calcium channel β subunit is essential for binding to the α subunit

The β subunits of voltage-dependent calcium channels bind the pore-forming α1 subunit and play an important role in the regulation of calcium channel function. Recently, we have identified a new splice variant of the β4 subunit, which we have termed the β4d subunit. The β4d subunit is a truncated splice variant of the β4b subunit and lacks parts of the guanylate kinase (GK) domain and the C-terminus. The calcium current in BHK cells expressing α1C and α2δ with the β4d subunit was as small as that without the β4d subunit. Western blot analysis revealed that β4d protein was expressed to a lesser extent that the β4b protein. In addition, a GST pull down assay showed that the β4d subunit could not interact with the α1 subunit of the calcium channel. Collectively, our results suggest that the GK domain of the β subunit is essential for the expression of the functional calcium channel.