Bernhard Flucher

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Physiology of Calcium Channels / Neuro-Muscular Physiology

Research: Structure and Function of Voltage-Gated Calcium Channels in Excitable Cells

Voltage-gated calcium channels are key regulators of vital cell functions such as contraction of heart and skeletal muscles, secretion of hormones and neurotransmitters, or the regulation of gene expression. Voltage-gated calcium channels function by opening their calcium-selective channel pore in response to changes of the membrane potential. The resulting influx of calcium ions into the cell depolarizes the plasma membrane and the transient rise in the cytoplasmic calcium concentration serves as second messenger activating a multitude of signaling pathways and cell functions. Our laboratory uses state-of-the-art molecular genetics, cell biology, electrophysiology, and high-resolution microscopy approaches to study calcium channel functions in muscle and nerve cells.

Excitation-Contraction Coupling: In skeletal and cardiac muscle voltage-gated calcium channels convert the incoming electrical signal into calcium release from intracellular stores that in turn triggers contraction. Our research emphasis on skeletal muscle calcium channels led to the identification of hitherto unnoticed channel isoforms and revealed molecular mechanisms involved in the targeting and assembly of the calcium channel subunits in the triad junction. Structure-function studies revealed the molecular basis of the unique biophysical properties of the skeletal muscle calcium channel.

Synapse formation and synaptic plasticity: In synapses presynaptic calcium channels control the release of neurotransmitter in response to action potentials and postsynaptic calcium channels are involved in mechanisms of synaptic plasticity. Research in our laboratory is concerned with the assembly and composition of synaptic calcium channel complexes and the contribution of specific channel subunits to the development and function of synapses. Recent findings revealed a role of an auxiliary calcium channel subunit in the transcriptional regulation of other synaptic ion channel genes.

Calcium channels and disease: The essential functions of voltage-gated calcium channels in important physiological processes are mirrored by a broad range of disorders related to aberrant calcium channel functions. Channelopathies studied in our laboratory include dystrophic myotonia, cerebellar ataxia, and diabetes.

 

group1Joint research groups of Bernhard Flucher and Gerald Obermair (link)

 

Ongoing Research

  • The role of calcium channels in acetylcholine receptor pre-patterning during neuromuscular junction development
  • Expression and function of the skeletal muscle calcium channel splice variant CaV1.1DE29.
  • The molecular mechanisms regulating voltage-sensitivity of CaV1 calcium channels.
  • Bernhard Flucher heads the FWF-funded PhD program Molecular Cellular Biology & Oncology (MCBO)

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News

New FWF Project, article at mypoint, 2017  Anklick_Icon

 

Latest Publications

 

Book_Publication_IconFindeisen, F., Campiglio, M., Jo, H., Rumpf, C.H., Pope, L., Abderemane-Ali, F., Rossen, N.D., Flucher, B.E., DeGrado, W.F., and Minor, D.L. Jr (2017) Stapled voltage-gated calcium channel (CaV) α-interaction domain (AID) peptides act as selective protein-protein interaction inhibitors of CaV function. ACS Chem. Neurosci., 2017 Mar 17. doi: 10.1021/acschemneuro.6b00454. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28278376

 

Book_Publication_IconMastrolia, V., Flucher, S.M., Obermair, G.J., Drach, M., Hofer, H., Renström, E., Schwartz, A., Striessnig, J., Flucher, B.E., and Tuluc, P. (2017) Loss of α2δ-1 calcium channel subunit function increases the susceptibility for diabetes. Diabetes, 2017 Jan 23. pii: db151349. doi: 10.2337/db16-0336. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28115397

 

Book_Publication_IconCampiglio, M. and Flucher, B.E. (2017) STAC3 stably interacts through its C1 domain with CaV1.1 in skeletal muscle triads. Sci. Rep., 7:41003. doi: 10.1038/srep41003; https://www.ncbi.nlm.nih.gov/pubmed/28112192

 

Book_Publication_IconFlucher, B.E. and Tuluc, P. (2017) How and why are calcium currents curtailed in the skeletal muscle voltage-gated calcium channels? J. Physiol., 595:1451-1463. https://www.ncbi.nlm.nih.gov/pubmed/27896815

 

Book_Publication_IconStanika, R., Campiglio, M., Pinggera, A., Lee, A., Striessnig, J.,  Flucher, B.E., and Obermair, G.J. (2016) Splice variants of the Cav1.3 L-type calcium channel regulate dendritic spine morphology. Sci. Rep., 2016 Oct 6;6:34528. doi: 10.1038/srep34528; https://www.ncbi.nlm.nih.gov/pubmed/27708393

 

Book_Publication_IconFlucher, B.E. (2016) Specific contributions of the four voltage-sensing domains in L-type calcium channels to gating and modulation J. Gen. Physiol. 148:91-95. https://www.ncbi.nlm.nih.gov/pubmed/27481711

 

Book_Publication_IconRzhepetskyy, Y., Lazniewska, J., Proft, J.,  Campiglio, M., Flucher, B.E., and Weiss, N. (2016) A CaV3.2/Stac1 molecular complex controls T-type channel expression at the plasma membrane. Channels, 10:346-354. https://www.ncbi.nlm.nih.gov/pubmed/27149520

 

Book_Publication_IconTuluc, P., Benedetti, B., Coste de Bagneaux, P., Grabner, M., and Flucher, B.E. (2016) Two distinct voltage sensing domains control voltage-sensitivity and kinetics of current activation in CaV1.1 calcium channels. J. Gen. Physiology, 147:437-449. https://www.ncbi.nlm.nih.gov/pubmed/27185857

 

Book_Publication_IconBenedetti, B., Benedetti, A., and Flucher, B.E. (2016) Loss of the calcium channel β4 subunit impairs parallel fiber volley and purkinje cell firing in cerebellum of adult ataxic mice. Eur.  J. Neurosci. 43:1486-1498. https://www.ncbi.nlm.nih.gov/pubmed/27003325

 

Book_Publication_IconFlucher, B.E. (2016) Retrograde coupling: Muscle’s orphan signaling pathway? Biophs. J. 110:870-871. https://www.ncbi.nlm.nih.gov/pubmed/26910422

 

Book_Publication_IconSultana, N., Dienes, B., Benedetti, A., Tuluc, P., Szentesi, P., Sztretye, M., Rainer, J., Hess, M.W., Schwarzer, C., Obermair, G.J., Csernoch, L., and Flucher, B.E. (2016) Restricting calcium currents is required for correct fiber type specification in skeletal muscle. Development, 143:1547-1559. https://www.ncbi.nlm.nih.gov/pubmed/26965373

 

Book_Publication_IconTuluc, P., Yarov-Yarovoi, V., Benedetti, B., and Flucher, B.E. (2015) Molecular interactions in the voltage sensor controlling gating properties of CaV calcium channels. Structure, 24:261-271. https://www.ncbi.nlm.nih.gov/pubmed/26749449

 

Book_Publication_IconKaur, G., Pinggera, A., Ortner, N.J., Lieb, A., Sinnegger-Brauns, M.J., Yarov-Yarovoy, V., Obermair, G.J., Flucher, B.E., Striessnig, J. (2015) A polybasic plasma membrane binding motif in the I-II linker stabilizes voltage-gated Cav1.2 calcium channel function. J. Biol. Chem. 290:21086-100. https://www.ncbi.nlm.nih.gov/pubmed/26100638

 

Book_Publication_IconFlucher, B.E. (2015) How is SR calcium release in muscle modulated by PIP(4,5)2? J. Gen. Physiol. 145:361-364. https://www.ncbi.nlm.nih.gov/pubmed/25918356



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