Ca 2+ signaling of pancreatic acinar cells in malignant hyperthermia susceptibility

Malignant hyperthermia susceptibility (MHS) and acute pancreatitis (AP) share a common cellular pathomechanism that is Ca -overload of the muscle fiber and the pancreatic acinar cell (PAC). In the muscle, gain-of-function mutations of the ryanodine receptor (RyR1) make the Ca -release mechanism hype...

Full description

Saved in:
Bibliographic Details
Published in:Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2024-12, Vol.24 (8), p.1257
Main Authors: Geyer, Nikolett, Diszházi, Gyula, Magyar, Zsuzsanna É, Dienes, Beatrix, Csáki, Réka, Enyedi, Péter, Madácsy, Tamara, Maléth, József, Almássy, János
Format: Article
Language:English
Subjects:
Acinar Cells - metabolism
Animals
Calcium - metabolism
Calcium Signaling
Ceruletide
Male
Malignant Hyperthermia - genetics
Malignant Hyperthermia - metabolism
Mice
Mice, Inbred C57BL
Mutation
Pancreas - metabolism
Pancreas - pathology
Pancreatitis - chemically induced
Pancreatitis - metabolism
Pancreatitis - pathology
Ryanodine Receptor Calcium Release Channel - genetics
Ryanodine Receptor Calcium Release Channel - metabolism
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Malignant hyperthermia susceptibility (MHS) and acute pancreatitis (AP) share a common cellular pathomechanism that is Ca -overload of the muscle fiber and the pancreatic acinar cell (PAC). In the muscle, gain-of-function mutations of the ryanodine receptor (RyR1) make the Ca -release mechanism hypersensitive to certain ligands, including Ca , volatile anaesthetics and succinylcholine, creating a medical emergency when the patient is exposed to these drugs. As RyR1 was shown to contribute to Ca -overload in PAC, we presumed that pancreata of MHS individuals are more prone to AP. Accordingly, a recent case study reported coincidence of MHS with recurrent AP, indicating a pathological link between the two diseases. We tested if MHS poses a risk for AP in mice carrying the Y522S MHS mutation. Fluorescent Ca imaging was performed in PACs. Conventional histopathological analysis and plazma amylase measurement was performed using a cerulein-induced pancreatitis mouse model. The intracellular Ca -signals of PACs from MHS mice were slightly bigger then in wild type when stimulated with 0.2 and 2 μM carbachol (cch) or with 1 and 5 mM bile acid (taurocholic acid). Store-operated-Ca -entry was also higher in PACs from MHS mice. Nevertheless, histopathological analysis and plasma amylase levels did not indicate more severe AP in MHS. These results suggest that the Y522S RyR1 mutation alter the Ca -homeostasis in PACs, but not as much as to cause or aggravate AP.
ISSN:1424-3911