title: COOH-terminal truncated alpha(1S) subunits conduct current better than full-length dihydropyridine receptors.
abstract: Skeletal muscle dihydropyridine (DHP) receptors function both as voltage-activated Ca(2+) channels and as voltage sensors for coupling membrane depolarization to release of Ca(2+) from the sarcoplasmic reticulum. In skeletal muscle, the principal or alpha(1S) subunit occurs in full-length ( approximately 10% of total) and post-transcriptionally truncated ( approximately 90%) forms, which has raised the possibility that the two functional roles are subserved by DHP receptors comprised of different sized alpha(1S) subunits. We tested the functional properties of each form by injecting oocytes with cRNAs coding for full-length (alpha(1S)) or truncated (alpha(1SDeltaC)) alpha 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 alpha(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 Ba(2+) currents were small relative to Q(max). The truncated alpha(1SDeltaC) 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 alpha(1S) subunit conduct the majority of the L-type Ca(2+) current in skeletal muscle. Our data also suggest that the carboxyl terminus of the alpha(1S) subunit modulates the coupling between charge movement and channel opening.
authors.affiliation: Program in Neuroscience, Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Morrill
authors.forename: S C
authors.initials: SC
authors.lastname: Cannon
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007700:Kinetics; D008564:Membrane Potentials; D018482:Muscle, Skeletal / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D020746:Calcium Channels, L-Type; D018076:DNA, Complementary; D010446:Peptide Fragments; D011994:Recombinant Proteins