Striessnig Jörg, Univ.-Prof. Dr.

University / Clinic: University of Innsbruck
Institute: Dept. of Pharmacology and Toxicology, Inst. of Pharmacy
Research Area: voltage-gated calcium channels


Research Topic:
Our research interest is to reveal the physiology, pharmacology and pharmacotherapeutic potential of voltage-gated Ca2+-channels. We also study how Ca2+-channel dysfunction may lead to diseases such as inherited forms of migraine and eye or inner ear disturbances. купить подушку

At present we mainly focus on the physiological role, the pharmacological and biophysical properties of Cav1.3 calcium channels. These channels are present at much lower abundance in most neuronal, endocrine and muscle cells than other L-type channel subunits. Interestingly, the biophysical properties of Cav1.3 allow it to serve pacemaker functions in brain and heart. We study the effects of alternative splicing on channel function, its modulation by neurotransmitters, enzymes and drugs and its expression in different tissues. We described the consequences of its gene-knockout recently. In addition to Cav1.3 knockout mice another novel mouse model has been generated by our group which will allow to determine the physiological role of Cav1.3 and the pharmacological consequences of its selective activation in vivo. In addition, we are currently identifying proteins associated with calcium channel complexes which may participate in calcium channel signal transduction and channel fine-tuning.купить подушку киев

  Cav1.3 L-type Ca2+ channel dysfunction in autism spectrum disorders
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Selected publications:
  Mastrolia V, Flucher S, Obermair G, Drach M, Hofer H, Renström E, Schwartz A, Striessnig J, Flucher B, Tuluc P
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]

  Monteleone S, Lieb A, Pinggera A, Negro G, Fuchs JE, Hofer F, Striessnig J, Tuluc P, Liedl KR
Mechanisms Responsible for ω-Pore Currents in Cav Calcium Channel Voltage-Sensing Domains
Biophysical Journal 113, Nr. 7 (3. Oktober 2017): 1485–95

  Ortner NJ, Bock G, Dougalis A, Kharitonova M, Duda J, Hess S, Tuluc P, Pomberger T, Stefanova N, Pitterl F, Ciossek T, Oberacher H, Draheim HJ, Kloppenburg P, Liss B, Striessnig J
Lower Affinity of Isradipine for L-Type Ca(2+) Channels during Substantia Nigra Dopamine Neuron-Like Activity: Implications for Neuroprotection in Parkinson’s Disease
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 37, Nr. 28 (12. Ju

  Pinggera, A, Mackenroth L, Rump A, Schallner J, Beleggia F, Wollnik B, Striessnig J
New Gain-of-Function Mutation Shows CACNA1D as Recurrently Mutated Gene in Autism Spectrum Disorders and Epilepsy
Human Molecular Genetics, 4. Mai 2017

  Tan GC, Negro G, Pinggera A, Tizen Laim NMS, Mohamed Rose I, Ceral J, Ryska A, Chin LK, Kamaruddin NA, Mohd Mokhtar N, A Jamal AR, Sukor N, Solar M, Striessnig J, Brown MJ, Azizan EA

Hypertension (Dallas, Tex.: 1979), 5. Juni 2017

  Pinggera A, Striessnig J
Cav 1.3 (CACNA1D) L-type Ca2+ channel dysfunction in CNS disorders.
J Physiol. 2016 Feb 4. doi: 10.1113/JP270672.

  Stanika R, Campiglio M, Pinggera A, Lee A, Striessnig J, Flucher B, Obermair G
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

  Pinggera A, Lieb A, Benedetti B, Lampert M, Monteleone S, Liedl K, Tuluc P, Striessnig J
CACNA1D de novo mutations in autism spectrum disorders activate Cav1.3 L-type calcium channels.
Biol Psychiatry. 2015 May 1;77(9):816-22.

  Kaur G, Pinggera A, Ortner N, Lieb A, Sinnegger-Brauns M, Yarov-Yarovoy V, Obermair G, Flucher B, Striessnig J
A Polybasic Plasma Membrane Binding Motif in the I-II Linker Stabilizes Voltage-Gated Cav1.2 Calcium Channel Function.
J Biol Chem. 2015 Aug 21;290(34):21086-100.

  Ortner N, Striessnig J
L-type calcium channels as drug targets in CNS disorders.
Channels (Austin). 2016;10(1):7-13.

  Striessnig J, Ortner N, Pinggera A
Pharmacology of L-type calcium channels: novel drugs for old targets?
Curr Mol Pharmacol. 2015;8(2):110-22.

  Lieb A, Ortner N, Striessnig J
C-terminal modulatory domain controls coupling of voltage-sensing to pore opening in Cav1.3 L-type Ca(2+) channels.
Biophys J. 2014 Apr 1;106(7):1467-75.

  Striessnig J, Pinggera A, Kaur G, Bock G, Tuluc P
L-type Ca2+ channels in heart and brain.
Wiley Interdiscip Rev Membr Transp Signal. 2014 Mar 1;3(2):15-38.

  Ortner NJ, Bock G, Vandael DH, Mauersberger R, Draheim HJ, Gust R, Carbone E, Tuluc P, Striessnig J
Pyrimidine-2,4,6-triones are a new class of voltage-gated L-type Ca2+ channel activators.
Nature communications

  Lieb A, Scharinger A, Sartori S, Sinnegger-Brauns M, Striessnig J
Structural determinants of CaV1.3 L-type calcium channel gating.
Channels (Austin). 2012 May-Jun;6(3):197-205

  Bock G, Gebhart M, Scharinger A, Jangsangthong W, Busquet P, Poggiani C, Sartori S, Mangoni M, Sinnegger-Brauns M, Herzig S, Striessnig J, Koschak A
Functional properties of a newly identified C-terminal splice variant of Cav1.3 L-type Ca2+ channels.
J Biol Chem. 2011 Dec 9;286(49):42736-48.

  Baig S, Koschak A, Lieb A, Gebhart M, Dafinger C, Nürnberg G, Ali A, Ahmad I, Sinnegger-Brauns M, Brandt N, Engel J, Mangoni M, Farooq M, Khan H, Nürnberg P, Striessnig J, Bolz H
Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy with bradycardia and congenital deafness.
Nat Neurosci. 2011 Jan;14(1):77-84.

  Gebhart M, Juhasz-Vedres G, Zuccotti A, Brandt N, Engel J, Trockenbacher A, Kaur G, Obermair G, Knipper M, Koschak A, Striessnig J
Modulation of Ca(v)1.3 Ca(2+) channel gating by Rab3 interacting molecule
Mol Cell Neurosci. 2010 Jul;44(3):246-59.

  Striessnig J, Bolz HJ, Koschak A (2010)
Channelopathies in Cav1.1, Cav1.3, and Cav1.4 voltage-gated L-type Ca2+ channels
Pflüger's Arch 460:361-374

  Subramanyam P, Obermair G, Baumgartner S, Gebhart M, Striessnig J, Kaufmann W, Geley S, Flucher B
Activity and calcium regulate nuclear targeting of the calcium channel beta4b subunit in nerve and muscle cells
Channels 5:343-55.

  Singh A, Gebhart M, Fritsch R, Sinnegger-Brauns M, Poggiani C, Hoda J, Engel J, Romanin C, Striessnig J, Koschak A
Modulation of voltage- and Ca2+-dependent gating of Cav1.3 L-type calcium channels by alternative splicing of a C-terminal regulatory domain.
J Biol Chem 283:20733-44

  Busquet P, Hetzenauer A, Sinnegger-Brauns M, Striessnig J, Singewald N
Role of L-type Ca2+ channel isoforms in the extinction of conditioned fear
Learn Mem 15:378-86.

  Singh A, Hamedinger D, Hoda J, Gebhart M, Koschak A, Romanin C, Striessnig J
C-terminal modulator controls Ca2+-dependent gating of Ca(v)1.4 L-type Ca2+ channels.
Nat Neurosci., 9, 1108-16.

  Hoda J, Zaghetto F, Singh A, Koschak A, Striessnig J
Effects of congenital stationary night blindness type 2 mutations R508Q and L1364H on Cav1.4 L-type Ca2+ channel function and expression.
J Neurochem., 96, 1648-58.

  Striessnig J, Koschak A, Sinnegger-Brauns M, Hetzenauer A, Nguyen N, Busquet P, Pelster G, Singewald N
Role of voltage-gated L-type Ca2+ channel isoforms for brain function
Biochem Soc Trans. 2006 Nov;34(Pt 5):903-9.

  Hoda J, Zaghetto F, Koschak A, Striessnig J
CSNB2 mutations S229P, G369D, L1068P, and W1440X alter channel gating or functional expression of Cav1.4 L-type Ca2+ channels
J Neurosci 25: 252-259

  Sinnegger-Brauns M, Hetzenauer A, Huber I, Renström E, Wietzorrek G, Berjukov S, Cavalli M, Walter D, Koschak A, Waldschütz R, Hering S, Bova S, Rorsman P, Pongs O, Singewald S, Striessnig J
Isoform-specific regulation of mood behavior and pancreatic beta cell and cardiovascular function by L-type Ca 2+ channels
J Clin Invest 113: 1430-1439

  Koschak A, Reimer D, Huber I, Grabner M, Glossmann H, Engel J, Striessnig J
Alpha1D (Cav1.3) subunits can form L-type Ca2+ channels activating at negative voltages
J Biol Chem, 276: 22100 - 22106

  Platzer J, Engel J, Schrott-Fischer A, Stephan K, Bova S, Chen H, Zheng H, Striessnig J
Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels
Cell 102: 89-97