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.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology