Cooh-Terminal Truncated Alpha_1S Subunits Conduct Current Better than Full-Length Dihydropyridine Receptors

Skeletal muscle dihydropyridine (DHP) receptors function both as voltage-activated Ca²⁺ channels and as voltage sensors for coupling membrane depolarization to release of Ca²⁺ from the sarcoplasmic reticulum. In skeletal muscle, the principal or α_1S subunit occurs in full-length (∼10% of total) and post-transcriptionally truncated (∼90%) forms, which has raised the possibility that the two functional roles are subserved by DHP receptors comprised of different sized α_1S subunits. We tested the functional properties of each form by injecting oocytes with cRNAs coding for full-length (α_1S) or truncated (α_1SΔC) α subunits. Both translation products were expressed in the membrane, as evidenced by increases in the gating charge (Q_max 80–150 pC). Thus, oocytes provide a robust expression system for the study of gating charge movement in α_1S, unencumbered by contributions from other voltage-gated channels or the complexities of the transverse tubules. As in recordings from skeletal muscle, for heterologously expressed channels the peak inward Ba²⁺ currents were small relative to Q_max. The truncated α_1SΔC protein, however, supported much larger ionic currents than the full-length product. These data raise the possibility that DHP receptors containing the more abundant, truncated form of the α_1S subunit conduct the majority of the L-type Ca²⁺ current in skeletal muscle. Our data also suggest that the carboxyl terminus of the α_1S subunit modulates the coupling between charge movement and channel opening.