{
  "@type": "dcat:Dataset",
  "accessLevel": "public",
  "bureauCode": [
    "009:25"
  ],
  "contactPoint": {
    "@type": "vcard:Contact",
    "fn": "NIH",
    "hasEmail": "mailto:info@nih.gov"
  },
  "description": "Background\n          The L-type Ca2+ channel formed by the dihydropyridine receptor (DHPR) of skeletal muscle senses the membrane voltage and opens the ryanodine receptor (RyR1). This channel-to-channel coupling is essential for Ca2+ signaling but poorly understood. We characterized a single-base frame-shift mutant of α1S, the pore subunit of the DHPR, that has the unusual ability to function voltage sensor for excitation-contraction (EC) coupling by virtue of expressing two complementary hemi-Ca2+ channel fragments.\n        \n        \n          Results\n          Functional analysis of cDNA transfected dysgenic myotubes lacking α1S were carried out using voltage-clamp, confocal Ca2+ indicator fluoresence, epitope immunofluorescence and immunoblots of expressed proteins. The frame-shift mutant (fs-α1S) expressed the N-terminal half of α1S (M1 to L670) and the C-terminal half starting at M701 separately. The C-terminal fragment was generated by an unexpected restart of translation of the fs-α1S message at M701 and was eliminated by a M701I mutation. Protein-protein complementation between the two fragments produced recovery of skeletal-type EC coupling but not L-type Ca2+ current.\n        \n        \n          Discussion\n          A premature stop codon in the II-III loop may not necessarily cause a loss of DHPR function due to a restart of translation within the II-III loop, presumably by a mechanism involving leaky ribosomal scanning. In these cases, function is recovered by expression of complementary protein fragments from the same cDNA. DHPR-RyR1 interactions can be achieved via protein-protein complementation between hemi-Ca2+ channel proteins, hence an intact II-III loop is not essential for coupling the DHPR voltage sensor to the opening of RyR1 channel.",
  "distribution": [
    {
      "@type": "dcat:Distribution",
      "description": "Visit the original government dataset for complete information, documentation, and data access.",
      "downloadURL": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC64647/",
      "mediaType": "text/html",
      "title": "Official Government Data Source"
    }
  ],
  "identifier": "https://healthdata.gov/api/views/4p7i-233u",
  "issued": "2025-07-14",
  "keyword": [
    "dihydropyridine-receptor",
    "excitation-contraction-coupling",
    "nih",
    "ryanodine-receptor",
    "voltage-clamp"
  ],
  "landingPage": "https://healthdata.gov/d/4p7i-233u",
  "modified": "2025-09-06",
  "programCode": [
    "009:033"
  ],
  "publisher": {
    "@type": "org:Organization",
    "name": "National Institutes of Health"
  },
  "theme": [
    "NIH"
  ],
  "title": "Functional analysis of a frame-shift mutant of the dihydropyridine receptor pore subunit (α"
}