Inactivation of L-type calcium channels is determined by the length of the N terminus of mutant β 1 subunits

Voltage-dependent calcium channel (Ca v ) pores are modulated by cytosolic β subunits. Four β-subunit genes and their splice variants offer a wide structural array for tissue- or disease-specific biophysical gating phenotypes. For instance, the length of the N terminus of β 2 subunits has major effects on activation and inactivation rates. We tested whether a similar mechanism principally operates in a β 1 subunit. Wild-type β 1a subunit (N terminus length 60 aa) and its newly generated N-terminal deletion mutants (51, 27 and 18 aa) were examined within recombinant L-type calcium channel complexes (Ca v 1.2 and α 2 δ2) in HEK293 cells at the whole-cell and single-channel level. Whole-cell currents were enhanced by co-transfection of the full-length β 1a subunit and by all truncated constructs. Voltage dependence of steady-state activation and inactivation did not depend on N terminus length, but inactivation rate was diminished by N terminus truncation. This was confirmed at the single-channel level, using ensemble average currents. Additionally, gating properties were estimated by Markov modeling. In confirmation of the descriptive analysis, inactivation rate, but none of the other transition rates, was reduced by shortening of the β 1a subunit N terminus. Our study shows that the length-dependent mechanism of modulating inactivation kinetics of β 2 calcium channel subunits can be confirmed and extended to the β 1 calcium channel subunit.