COOH-terminal truncated alpha(1s) subunits conduct current better than full-length dihydropyridine receptors

James A. Morrill, Stephen C. Cannon

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)341-348
Number of pages8
JournalJournal of General Physiology
Volume116
Issue number3
DOIs
StatePublished - 2000

Keywords

  • Ca channels
  • Cut-open oocyte voltage clamp
  • Gating charge movement
  • Skeletal muscle
  • Xenopus oocyte expression

ASJC Scopus subject areas

  • Physiology

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