Anesthetics; Calcium; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Malignant Hyperthermia; Patch-Clamp Techniques; Ryanodine Receptor Calcium Release Channel
My general research interest is the effects of anesthetics on ion channels. This includes not only the mechanism how anesthetics cause general anesthesia but also adverse side effects of certain anesthetics which have their origin out side the general nervous system. Malignant hyperthermia (MH) is an inherited pharmacological disorder which is in most cases the result of mutations in the ryanodine receptor (RYR1) and can be triggered by volatile anesthetics leading to an uncontrolled Ca2+ release in the skeletal muscle during general anesthesia which might lead to a fatal outcome. Mapping the ryanodine receptors of susceptible Austrian MH patients and the proof that an identified RYR1 mutation is causative for MH is our main task.
Beside that I am interested in the effect of general anesthetics on the G-protein coupled inwardly rectifying potassium channels. These channels ar located not only in the central nervous system but also in other organ systems and their pharmacological modulation might explain some side effects of general anesthetics.
Techniques, methods & infrastructure
In vitro investigations of cultured cells are the main source for our experimental research. Primary cultured muscle cells but also cell lines and cellular expression systems, including Xenopus oocytes are applied. Standard laboratory techniques such as western blotting, PCR, qPCR and FACS analyses are available. Main focus lies on Ca2+ imaging and cellular electrophysiology, including functional analysis of single channels.
- Kaufmann, A. et al., 2012. Novel Double and Single Ryanodine Receptor 1 Variants in Two Austrian Malignant Hyperthermia Families. Anesthesia & Analgesia, 114(5), pp.1017-1025. Available at: http://dx.doi.org/10.1213/ANE.0b013e31824a95ad.
- Weigl, L.G. and Schreibmayer, W., 2001 G Protein-Gated Inwardly Rectifying Potassium Channels Are Targets for Volatile Anesthetics
- Lacava, C. et al., 2012. 3,5-Di-t-butyl catechol is a potent human ryanodine receptor 1 activator, not suitable for the diagnosis of malignant hyperthermia susceptibility. Pharmacological Research, 66(1), pp.80-87. Available at: http://dx.doi.org/10.1016/j.phrs.2012.03.012.
- Steinecker-Frohnwieser, B. et al., 2014. The disease modifying osteoarthritis drug diacerein is able to antagonize pro inflammatory state of chondrocytes under mild mechanical stimuli. Osteoarthritis and Cartilage, 22(7), pp.1044-1052. Available at: http://dx.doi.org/10.1016/j.joca.2014.05.008.
- Kaufmann, A. et al., 2008. Novel Ryanodine Receptor Mutation That May Cause Malignant Hyperthermia. Anesthesiology, 109(3), pp.457-464. Available at: http://dx.doi.org/10.1097/ALN.0b013e318182a93b.