The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
Full Papers
Novel Mutations in C-terminal Channel Region of the Ryanodine Receptor in Malignant Hyperthermia Patients
Hideto OyamadaKeiko OguchiNaoto SaitohToshiko YamazawaKenzo HiroseYoko KawanaKazunao WakatsukiKatsuji OguchiMegumi TagamiKazuo HanaokaMakoto EndoMasamitsu Iino
Author information
JOURNALS FREE ACCESS

Volume 88 (2002) Issue 2 Pages 159-166

Details
Download PDF (385K) Contact us
Abstract

Malignant hyperthermia (MH) is a pharmacogenetical complication of general anesthesia resulting from abnormal Ca2+-induced Ca2+ release (CICR) via the type 1 ryanodine receptor (RyR1) in skeletal muscles. In this study, we analyzed the genomic DNAs prepared for determination of all the 106 exons of the RyR1 gene from blood samples donated by two MH patients with extremely high CICR rates in their biopsied skeletal muscles and a clear history of MH incidence. Two novel point mutations were found in the exons 96 and 101 with alterations in the coded amino acids within the C-terminal channel region, i.e., Pro4668 to Ser and Leu4838 to Val. The latter mutation was found in both MH patients. Rabbit RyR1 channels carrying corresponding mutations were expressed in CHO cells for functional assay. It was found that the L to V but not the P to S mutation of the RyR1 resulted in enhanced Ca2+ release activity. These results indicate that the L4838V mutation is responsible for the MH incidence. The L4838V mutation is unique because it is the mutation first found within a hydrophobic transmembrane segment of the channel region and should provide further information on the function of the RyR1 as well as for genetic diagnosis of MH.

Information related to the author
© The Japanese Pharmacological Society 2002
Previous article Next article

Recently visited articles
feedback
Top