Institute of Neurophysiology


Medical Faculty
University of Cologne

Prof. Dr. Toni Schneider
Email:
Phone: +49-221-478-6946
Fax:      +49-221-478-6965

Students UK-online

Doctoral thesis

 

Research interests

• Channelopathies (Ionenkanal-Krankheiten) are caused by defects either in an ion conducting or an associated auxiliary subunit of the channel. We are focused on structure and function of a voltage-dependent Ca2+-channel containing the Cav2.3 E-type subunit, the formerly called “pharmacoresistant” (R-type) calcium channel. Its gene inactivation has given us access to its physiological function which is related to the cardiac, the endocrine and the neuronal system. Protein interaction partners of the channel protein have been detected. They connect ion channel activity with cellular functions helping us to explore molecular mechanisms of channelopathies related to arrhythmia, hormone release dysfunction, and neuronal disorders like epilepsy.

Current research projects:

• Cardiac arrhythmia                                          (Coworkers, Dr. Dr. Marco Weiergräber, Renate Clemens, Dipl.-Biol. Margit Henry, cand. med. Thomas Galetin)

• Rhythm generation and synchronization    (Coworkers, Dr. Dr. Marco Weiergräber, Renate Clemens, Dipl.-Biol. Margit Henry, cand. med. Nora Matar)
• Secretion & neurotransmitter release           (Dr. Irina Drobinskaya, Arzt Andreas Krieger, cand.med. Marcel Kamp.)
• Interaction partners of R-type / E-type        (Coworkers, Arzt Andreas Krieger, cand. med. Marcel Kamp, Dipl.-Biol. Margit Henry
                                                                              Kayalvizhi Radhakrishnan)
• Retina                                                (Project in the "W. Sickel Laboratory of the Superfused Retina" in Cooperation with
                                                                              PD Dr. C. Lüke. Coworkers: cand. med. Siarhei Siapich, Arzt Herr Brandt,
                                                                              cand. med. dent. Thea Lingohr, cand. med. dent. Mehran Maghsoodian, cand. med. Mohammed Banat.
• Interaction partners of T-type                       (Coworker, Dipl.-Biol. Margit Henry, Kayalvizhi Radhakrishnan, Dipl.-Biol. Tamara Rotshteyn)

Publications

Matthias Lüke , Marco Weiergräber, Carl Brand, Siarhei A. Siapich, Mohammed Banat, Jürgen Hescheler, Christoph Lüke, Toni Schneider (2005)
The isolated perfused bovine retina - a sensitive tool for pharmacological research on retinal function . Brain Research Protocols, in press.

Matthias Lüke, Krott Ralf, Warga Max, Szurman Peter, Grisanti Salvatore, Bartz-Schmidt Karl Ulrich, Schneider Toni, Lüke Christoph (2005)
Effects of the Protein Tyrosine Kinase Inhibitor Genistein and Taurine on Retinal Function in Isolated Superfused Retina.
Graefes Archive for Clinical and Experimental Ophthalmology, in press

Matthias Lüke, Christoph Lüke, J. Hescheler, T. Schneider, W. Sickel^Â (2005) Effects of Phosphodiesterase Type 5 Inhibitor Sildenafil on Retinal Function in Isolated Superfused Retina. J. Ocul. Pharmacol. & Ther., 21: 305-14

Matthias Lüke, Margit Henry, Thea Lingohr, Mehran Maghsoodian, Jürgen Hescheler , Marco Weiergräber, Werner Sickel , Toni Schneider (2005) A Ni²⁺-sensitive component of the ERG-b-wave from the isolated bovine retina is related to E-type voltage-gated Ca²⁺ channels. Graefe Archive for Clinical and Experimental Ophthalmology, 243: 933-941. 

Marco Weiergräber, Margit Henry, Jürgen Hescheler, Neil Smyth & Toni Schneider (2005) Electrocorticographic and deep intracerebral EEG recording in mice using a telemetry system. Brain Res. & Brain Res. Protoc., 14: 154-64.

Kamp M.A., Krieger A., Henry M., Hescheler J. , Weiergräber M., Schneider T. (2005) Presynaptic “Ca_v 2.3 containing” E-type Ca²⁺ channels share dual roles during neurotransmitter release.  Eur J Neurosci. 21:1617-25. Review

Xingjun Jing, Dai-Qing Li, Charlotta S. Olofsson, Albert Salehi, Vikas V. Surve, José Caballero, Rosita Ivarsson, Ingmar Lundquist, Alexey Pereverzev, Toni Schneider, Patrik Rorsman and Erik Renström (2005) Cav2.3 calcium channels control second phase insulin release. J. Clin. Invest. 115: 146-154.

Marco Weiergräber, Margit Henry, Michael Südkamp, Ernst-Rainer de Vivie, Jürgen Hescheler, Toni Schneider (2005) Ablation of Ca_v2.3 / E-type voltage-gated calcium channel results in cardiac arrhythmia and altered autonomic control within the murine cardiovascular system. Basic Res. Cardiol. 100: 1-13.

Klöckner U., Pereverzev A, Leroy J, Krieger A, Vajna R, Pfitzer G, Hescheler J, Malécot CO, Schneider T (2004) The cytosolic II-III loop of Ca_v2.3 provides an essential determinant for the phorbol ester-mediated stimulation of E-type Ca²⁺ channel activity. Eur. J. Neurosci., 19, 2659-2668.

Jahn Holger & Schneider Toni (2004) Diabetes mellitus als Komplikation der Behandlung mit atypischen Neuroleptika. Mögliche Pathomechanismen und Therapieempfehlungen. Der Nervenarzt, 75, 442-50.

Zhong-Ju Lu, Alexey Pereverzev, Hui-Lin Liu, Marco Weiergräber, Margit Henry, Andreas Krieger, Neil Smyth, Jürgen Hescheler, Toni Schneider (2004) Arrhythmia in Isolated Prenatal Hearts after Ablation of the Ca_v2.3 (a1E) Subunit of Voltage-gated Ca²⁺ Channels. Cellul. Physiol. Biochem., 14, 11-22.

Jérôme Leroy, Alexey Pereverzev, Rolf Vajna, Ning Qin, Gabriele Pfitzer, Jürgen Hescheler, Claire Malécot, Toni Schneider, Udo Klöckner (2003) A novel Ca²⁺-dependent regulation of neuronal E-type Ca²⁺ channels is mediated by an arginine-rich region in the cytosolic II-III linker. Eur. J. Neurosci., 18, 841-855.

Atticus H. Hainsworth, Nicolle C McNaughton, Alexey Pereverzev, Toni Schneider, and Andrew D Randall (2003) Actions of sipatrigine, 202W92 and lamotrigine on R-type and T-type Ca²⁺ channel currents. Eur. J. Pharmacol. 467, 77 – 80.

Dirk Dietrich, Timo Kirschstein, Maria Kukley, Alexej Pereverzev, C. von der Brelie, Toni Schneider, Heinz Beck (2003) Functional specialization of presynaptic Ca_v2.3 Ca²⁺ channels. Neuron, 39, 483-496

Pereverzev Alexey, Jérôme Leroy, Claire Malécot, Gabriele Pfitzer, Jürgen Hescheler, Udo Klöckner, Toni Schneider (2002) Alternate Splicing in the Cytosolic II-III Loop and Carboxy Terminus of the human E-type voltage-gated Ca2+ channels. - Electrophysiological characterization of isoforms. Molec. Cellul. Neurosci. 21:352-65.

Sochivko Dmitry, Alexey Pereverzev, Neil Smyth, Cornelia Gissel, Toni Schneider, Heinz Beck (2002) The a1E Ca2+ channel subunit underlies R-type Ca2+ currents in hippocampal and cortical pyramidal neurons. J. Physiol., 542, 699-710.

Pereverzev Alexey , Marina Mikhna, Rolf Vajna, Cornelia Gissel, Margit Henry, Marco Weiergräber, Jürgen Hescheler, Neil Smyth, Toni Schneider (2002) Disturbances in glucose-tolerance, insulin-release and stress-induced hyperglycemia upon disruption of the Cav2.3 (a1E) subunit of voltage-gated Ca2+ channels. Mol. Endocrinol., 16, 884-95..

Pereverzev Alexey , Rolf Vajna, Gabriele Pfitzer, Jürgen Hescheler, Udo Klöckner, Toni Schneider (2002) Reduction of insulin secretion in the insulinoma cell line INS-1 by overexpression of a Ca2+ channel antisense-a1E cassette. Eur. J. Endocrinol., 146, 881-889.

Michels Guido, Jan Matthes, Renate Handrock, Ute Kuchinke, Ferdi Groner, Leanne L. Cribbs, Alexey Pereverzev, Toni Schneider, Edward Perez-Reyes and Stefan Herzig (2002) Single-channel pharmacology of mibefradil in human native T-type and recombinant Cav3.2 calcium channels. Mol. Pharmacol., 61, 682-694.

Vajna, R., Klöckner, U., Pereverzev, A., Weiergräber, M., Chen, X.-H., Miljanich, G., Klugbauer, N., Hescheler, J., Perez-Reyes, E., Schneider, T. (2001) Functional Coupling between 'R-Type' Ca2+ channels and insulin secretion in the insulinoma cell line INS-1. Eur. J. Biochem., 268, 1066-1075.

Weiergräber Marco, Alexey Pereverzev, Rolf Vajna, Margit Henry, Martin Schramm, Wolfgang Nastainczyk, Heike Grabsch, Toni Schneider (2000) Immunodetection of a1E Voltage-gated Ca2+ Channel in Chromogranin-positive Muscle Cells of Rat Heart, and in Distal Tubules of Human Kidney. J. Histochem. Cytochem. 48, 807-819.

Klöckner, U., Lee, J.-H., Cribbs, L.L., Daud, A., Hescheler, J., Pereverzev, A., Perez-Reyes, E., Schneider, T. (1999) Comparison of the Ca2+ currents induced by expression of three cloned a1 subunits, a1G, a1H, and a1I of low-voltage-activated T-type Ca2+ channels. Eur. J. Neurosci. 11, 4171-4178.

Nakashima, Y.M., Pereverzev, A., Schneider, T., Covey, D.F., Lingle, C.J. (1999) Blockade of Ba2+ current through human a1E channels by two steroid analogs, (+)-ACN and (+)-ECN. Neuropharmacology 38, 843-855.

Grabsch, H., Pereverzev, A., Weiergräber, M., Schramm, M., Henry, M., Vajna, R., Beattie, R., Volsen, S.G., Klöckner, U., Hescheler, J., Schneider T. (1999) Immunohistochemical Detection of a1E Voltage-gated Ca2+ Channel Isoforms in Cerebellum, INS-1 cells, and Neuroendocrine Cells of the Digestive System. J.Histochem.Cytochem. 47, 981-994.

Schramm, M., Vajna, R., Pereverzev, A., Tottene A., Tottene, A., Klöckner, U., Pietrobon, D., Hescheler, J., Schneider,T. (1999) Isoforms of alpha1E voltage-gated calcium channels in rat cerebellar granule cells. Detection of major calcium channel alpha1-transcripts by reverse transcription-polymerase chain reaction. Neuroscience 92, 565-575.

Jung-Ha Lee, Asif N. Daud, Leanne L. Cribbs, Antonio E. Lacerda, Alexei Pereverzev, Udo Klöckner, Toni Schneider, and Edward Perez-Reyes (1999) Cloning and expression of a novel member of the low-voltage-activated T-type calcium channel family. J. Neurosci., 19, 1912-1921.

Nakashima, Y.M., Todorovic, S.M., Pereverzev, A., Hescheler, J., Schneider, T., Lingle, C.J. (1998) Properties of Ba2+ currents arising from human a1E and a1Eß3 constructs expressed in HEK293 cells: physiology, pharmacology, and comparison to native T-type Ba2+ currents. Neuropharmacology, 37, 957-972.

Vajna, R., Schramm, M., Pereverzev, A., Arnhold, S., Grabsch, H., Klöckner, U., Perez-Reyes E., Hescheler, J., Schneider,T. (1998) New Isoform of the Neuronal Ca2+ Channel a1E Subunit in Islets of Langerhans and Kidney. Distribution of Voltage-Gated Ca2+ Channel a1 Subunits in Cell Lines and Tissues. Eur. J. Biochem. 257, 274-285.

Pereverzev, A., Köckner, U., Henry, M., Grabsch, H., Vajna, R., Olyschläger, S., Viatchenko-Karpinski, S., Schröder, R., Hescheler, J., Schneider T. (1998) Structural Diversity of Voltage-Dependent Ca2+ Channel a1E-Subunit. Eur. J. Neurosci., 10, 916-925.

Parent, L., Schneider, T., Moore, C. P., Talwar, D. (1997) Subunit regulation of the human brain a1E calcium channel. J. Membrane Biology, 160, 127 - 140.

Mehrke, G., Pereverzev, A., Grabsch, H., Hescheler, J., Schneider T. (1997) Receptor Mediated Modulation of Recombinant Neuronal Class E Calcium Channels. FEBS Lett. 408, 261-270

Schneider, T., Igelmund, P., Hescheler J. (1997) G Protein Interaction with K+ and Ca2+ Channels. Trends in Pharmacological Science, 18, 8-11.

Perez-Reyes, E., Schneider T. (1995) The Molecular Biology of Calcium Channels. Kidney International 48, 111-1124.

Wei, X.Y., S. Pan, H. Kim, T. Schneider, E. Perez-Reyes & L. Birnbaumer (1995) Multiple subunits are required for the high affinity and allosteric regulation of dihydropyridine binding to the cardiac L-type Ca2+ channels. J. Biol. Chem. 270, 27106-27111.

Schneider T., Perez-Reyes, E., Nyormoi, O., Wei, X., Crawford, G.D., Smith R.G., Appel, S.H., Birnbaumer, L. (1995). Alpha-1 Subunits of Voltage Gated Ca2+ Channels in the Mesen-cephalon x Neuroblastoma Hybrid Cell Line MES23.5. Neuroscience 68, 479-485.

Timchenko, L., Nastainczyk, W., Schneider, T., Hofmann, F., Caskey, C.T. (1995) Full-length myotonin protein kinase (72 kDa) displays serine kinase activity. Proc. Natl. Acad. Sci. USA 92, 5366 - 5370

Olcese, R., Qin, N., Schneider, T., Neely, A., Wei, X., Birnbaumer, L., Stefani, E. (1994) The Amino Terminus of a Calcium Channel ß Subunit Sets Rates of channel Inactivation Independently of the Subunit’s Effect on Activation. Neuron 13, 1433-1438

Perez-Reyes, E., Schneider T. (1994) Ca2+ channels: Structure, function, and classification. Drug Development Research 33, 295-318

Nyormoi, O., Schneider,T., Smith, R.G. (1994) A large scale preparative gel electrophoresis separation of a1 and a2 subunits of the voltage-gated Ca2+ channel from rabbit skeletal muscle. Electrophoresis, 15, 1183-1190.

Schneider T., X. Wei, Olcese, R., Costantin, J.L., Neely, A., Palade, P., Perez-Reyes, E., Qin, N., Zhou, J., Crawford, G.D., Smith, R.G., Appel, S.H., Stefani, E., Birnbaumer, L. (1994). Molecular analysis and functional expression of the human type E neuronal Ca2+-channel a1 subunit. Receptors and Channels 2, 255 - 270.

Kimura, F., R. G. Smith, O. Delbono, O. Nyormoi, T. Schneider, W. Nastainczyk, F. Hofmann, E. Stefani & S. H. Appel (1994) Amyotrophic lateral sclerosis patient antibodies label the Ca2+ channel a1 subunit. Ann. Neurol. 35, 164-171.

Smith, R.G., S. Hamilton, F. Hofmann, T. Schneider, W. Nastainczyk, L. Birnbaumer, E. Stefani & S. H. Appel (1992) Serum antibodies to L-type calcium channels in patients with amyo-tro-phic lateral sclerosis. N.Engl.J.Med. 327, 1721-1728.

Regulla, S., T. Schneider, W. Nastainczyk, H. E. Meyer & F. Hofmann (1991) Identification of the site of interaction of the dihydropyridine channel blockers nitrendipine and azidopine with the calcium- channel a1 subunit. EMBO J. 10, 45-49.

Schneider, T., S. Regulla & F. Hofmann (1991) The devapamil-binding site of the purified skeletal muscle receptor for organic-calcium channel blockers is modulated by micromolar and millimolar concentrations of Ca2+. Eur.J.Biochem. 200, 245-253.

Hofmann, F., V. Flockerzi, W. Nastainczyk, P. Ruth & T. Schneider (1990) The molecular structure and regulation of muscular calcium channels. Curr.Top.Cell Regul. 31, 223-239.

Hofmann, F., T. Schneider, A. Röhrkasten, W. Nastainczyk, M. Sieber, P. Ruth & V. Flockerzi (1989) Calcium channels: structure and function of receptors for calcium channel blockers in skeletal muscle. Arzneimittelforschung. 39, 164-168.

Hofmann F. & Schneider T. (1989) Calcium Channels: Structure and Function of the Skeletal Muscle Calcium Antagonist Receptor. In: Kotyk A. et al. (eds.) Highlights Modern Biochem. 1, 361-368

Jahn, H., W. Nastainczyk, A. Röhrkasten, T. Schneider & F. Hofmann (1988) Site-specific phosphorylation of the purified receptor for calcium-channel blockers by cAMP- and cGMP-dependent protein kinases, protein kinase C, calmodulin-dependent protein kinase II and casein kinase II. Eur.J.Biochem. 178, 535-542.

Hofmann, F., H. J. Oeken, T. Schneider & M. Sieber (1988) The biochemical properties of L-type calcium channels. J.Cardiovasc.Pharmacol. 12 Suppl 1, S25-S30.

Schneider, T. & F. Hofmann (1988) The bovine cardiac receptor for calcium channel blockers is a 195-kDa protein. Eur.J.Biochem. 174, 369-375.

Hofmann F., Nastainczyk W., Röhrkasten A., Schneider T., Sieber M. (1987) Regulation of the L-type calcium channel. Trends in Pharmacol. Sci. 8, 393-398