{"@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 \u03b11S, 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 \u03b11S were carried out using voltage-clamp, confocal Ca2+ indicator fluoresence, epitope immunofluorescence and immunoblots of expressed proteins. The frame-shift mutant (fs-\u03b11S) expressed the N-terminal half of \u03b11S (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-\u03b11S 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 (\u03b1"}