The Neuronal β₄ Subunit Increases the Unitary Conductance of L-type Voltage-gated Calcium Channels in PC12 Cells

β subunits of voltage-gated calcium channels influence channel behavior in numerous ways, including enhancing the targeting of α ₁ subunits to the plasma membrane and shifting the voltage dependence of activation and inactivation. Of the four β subunits that have been identified, β₄ is of particular interest because mutation of its α₁ subunit interaction domain produces severe neurological defects. Its differential distribution in the hippocampus prompted us to examine whether this subunit was responsible for the heterogeneity of hippocampal L-type calcium channels. To study the functional effects of the β₄ subunit on native L-type calcium channels, we transfected β₄ cDNA subcloned out of embryonic hippocampal neurons into PC12 cells, a cell line that contains the β₁, β ₂, and β₃ subunits but not the β₄ subunit. Cell-attached single-channel recordings of L-type channel activity from untransfected and transfected PC12 cells compared with recordings obtained from hippocampal neurons revealed an effect of the β₄ subunit on single-channel conductance. L-type channels in untransfected PC12 cells had a significantly smaller conductance (19.8 picosiemens (pS)) than L-type channels in hippocampal neurons (22 pS). After transfection of β ₄, however, L-type single-channel conductance was indistinguishable between the two cell types. Our data suggest that calcium channel β ₄ subunits affect the conductance of L-type calcium channels and that native hippocampal L-type channels contain the β₄ subunit.