Ca2+ signaling of pancreatic acinar cells in malignant hyperthermia susceptibility

Geyer, Nikolett and Diszházi, Gyula and Magyar, Zsuzsanna Édua and Dienes, Beatrix and Csáki, Réka and Enyedi, Péter and Madácsy, Tamara and Maléth, József and Almássy, János (2024) Ca2+ signaling of pancreatic acinar cells in malignant hyperthermia susceptibility. PANCREATOLOGY, 24 (8). pp. 1257-1264. ISSN 1424-3903

Preview

Text PancreatologyGeyer_1-s2.0-S1424390324007907-main.pdf - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview

Abstract

Background: Malignant hyperthermia susceptibility (MHS) and acute pancreatitis (AP) share a common cellular pathomechanism that is Ca2+-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 Ca2+-release mechanism hypersensitive to certain ligands, including Ca2+, volatile anaesthetics and succinylcholine, creating a medical emergency when the patient is exposed to these drugs. As RyR1 was shown to contribute to Ca2+-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. Methods: We tested if MHS poses a risk for AP in mice carrying the Y522S MHS mutation. Fluorescent Ca2+ imaging was performed in PACs. Conventional histopathological analysis and plazma amylase measurement was performed using a cerulein-induced pancreatitis mouse model. Results: The intracellular Ca2+-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-Ca2+-entry was also higher in PACs from MHS mice. Nevertheless, histopathological analysis and plasma amylase levels did not indicate more severe AP in MHS. Conclusions: These results suggest that the Y522S RyR1 mutation alter the Ca2+-homeostasis in PACs, but not as much as to cause or aggravate AP.

Actions (login required)

Edit Item