TY  - JOUR
A1  - Hoppe, Kerstin
A1  - Hack, Guido
A1  - Lehmann–Horn, Frank
A1  - Jurkat–Rott, Karin
A1  - Wearing, Scott
A1  - Zullo, Alberto
A1  - Carsana, Antonella
A1  - Klingler, Werner
T1  - Hypermetabolism in B–lymphocytes from malignant hyperthermia susceptible individuals
T2  - Scientific reports
N2  - Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle metabolism which is characterized by generalized muscle rigidity, increased body temperature, rhabdomyolysis, and severe metabolic acidosis. The underlying mechanism of MH involves excessive Ca2+ release in myotubes via the ryanodine receptor type 1 (RyR1). As RyR1 is also expressed in B–lymphocytes, this study investigated whether cellular metabolism of native B–lymphocytes was also altered in MH susceptible (MHS) individuals. A potent activator of RyR1, 4–chloro–m–cresol (4-CmC) was used to challenge native B-lymphocytes in a real–time, metabolic assay based on a pH–sensitive silicon biosensor chip. At the cellular level, a dose–dependent, phasic acidification occurred with 4–CmC. The acidification rate, an indicator of metabolic activation, was significantly higher in B–lymphocytes from MHS patients and required 3 to 5 fold lower concentrations of 4–CmC to evoke similar acidification rates to MHN. Native B–lymphocytes from MHS individuals are more sensitive to 4–CmC than those from MHN, reflecting a greater Ca2+ turnover. The acidification response, however, was less pronounced than in muscle cells, presumably reflecting the lower expression of RyR1 in B–lymphocytes.
KW  - Diagnostic markers
KW  - Metabolic diseases
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46608
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-466081
SN  - 2045-2322
N1  - Rights and permissions: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
VL  - 6
IS  - Art. 33372
SP  - 1
EP  - 11
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -