| http://purl.uniprot.org/citations/29212769 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29212769 | http://www.w3.org/2000/01/rdf-schema#comment | "Malignant hyperthermia (MH) susceptibility has been recently linked to a novel variant of β1a subunit of the dihydropyridine receptor (DHPR), a channel essential for Ca2+ regulation in skeletal muscle. Here we evaluate the effect of the mutant variant V156A on the structure/function of DHPR β1a subunit and assess its role on Ca2+ metabolism of cultured myotubes. Using differential scanning fluorimetry, we show that mutation V156A causes a significant reduction in thermal stability of the Src homology 3/guanylate kinase core domain of β1a subunit. Expression of the variant subunit in β1-null mouse myotubes resulted in increased sensitivity to caffeine stimulation. Whole cell patch-clamp analysis of β1a-V156A-expressing myotubes revealed a -2 mV shift in voltage dependence of channel activation, but no changes in Ca2+ conductance, current kinetics, or sarcoplasmic reticulum Ca2+ load were observed. Measurement of resting free Ca2+ and Na+ concentrations shows that both cations were significantly elevated in β1a-V156A-expressing myotubes and that these changes were linked to increased rates of plasmalemmal Ca2+ entry through Na+/Ca2+ exchanger and/or transient receptor potential canonical channels. Overall, our data show that mutant variant V156A results in instability of protein subdomains of β1a subunit leading to a phenotype of Ca2+ dysregulation that partly resembles that of other MH-linked mutations of DHPR α1S subunit. These data prove that homozygous expression of variant β1a-V156A has the potential to be a pathological variant, although it may require other gene defects to cause a full MH phenotype."xsd:string |
| http://purl.uniprot.org/citations/29212769 | http://purl.org/dc/terms/identifier | "doi:10.1152/ajpcell.00187.2017"xsd:string |
| http://purl.uniprot.org/citations/29212769 | http://purl.uniprot.org/core/author | "Lopez J.R."xsd:string |
| http://purl.uniprot.org/citations/29212769 | http://purl.uniprot.org/core/author | "Perez C.F."xsd:string |
| http://purl.uniprot.org/citations/29212769 | http://purl.uniprot.org/core/author | "Aditya S."xsd:string |
| http://purl.uniprot.org/citations/29212769 | http://purl.uniprot.org/core/author | "Casarotto M.G."xsd:string |
| http://purl.uniprot.org/citations/29212769 | http://purl.uniprot.org/core/author | "Dulhunty A.F."xsd:string |
| http://purl.uniprot.org/citations/29212769 | http://purl.uniprot.org/core/author | "Eltit J.M."xsd:string |
| http://purl.uniprot.org/citations/29212769 | http://purl.uniprot.org/core/author | "Bodnar D."xsd:string |
| http://purl.uniprot.org/citations/29212769 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/29212769 | http://purl.uniprot.org/core/name | "Am J Physiol Cell Physiol"xsd:string |
| http://purl.uniprot.org/citations/29212769 | http://purl.uniprot.org/core/pages | "C323-C333"xsd:string |
| http://purl.uniprot.org/citations/29212769 | http://purl.uniprot.org/core/title | "Functional and structural characterization of a novel malignant hyperthermia-susceptible variant of DHPR-betapisub>1api/sub> subunit (CACNB1)."xsd:string |
| http://purl.uniprot.org/citations/29212769 | http://purl.uniprot.org/core/volume | "314"xsd:string |
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