Department of Neurophysiology and Neuropharmacology (Center for Physiology and Pharmacology)
Position: Associate Professor
E-Mail: hannes.todt@meduniwien.ac.at
Research Interests
Neuropharmacology, Neurophysiology
Principle Investigator(s)
Abstract
We are interested in exploring the structural underpinnings of ion channel function and drug block. We apply a combination of site-directed mutagenesis with molecular modeling. These efforts may finally allow computerized drug design for the treatment of ion channel dysfunction in the heart, skeletal muscle and the nervous system and optimize treatment of diseases like epilepsy and arrhythmias of the heart. Another research focus of my group is cardiovascular phenotyping in transgenic mouse models. The electrical activity of the heart can be monitored in vivo by electrocardiographic methods. This allows the assessment of ion channel function in the intact organism.
Techniques
We explore ion channel function by voltage and current clamp in single cells. To this end we express native and mutated ion channels in Xenopus laevis oocytes and in mammalian cells and study the function of these proteins by means of the two-electrode voltage clamp technique or the patch clamp technique. Furthermore, we study the cardiac electrophysiology of trangenic mice by ECG recordings and programmed electrical stimulation in anaesthetized animals.
Selected publications
- Zarrabi T, Cervenka R, Sandtner W, Lukacs P, Koenig X, Hilber K, Mille M, Lipkind GM, Fozzard HA, Todt H. (2010) A molecular switch between the outer and the inner vestibules of the voltage-gated Na+ channel. J Biol Chem, 285(50): 39458-39470
- Cervenka R, Zarrabi T, Lukacs P, Todt H (2010) The Outer Vestibule of the Na+ Channel–Toxin Receptor and Modulator of Permeation as Well as Gating Mar Drugs, 8 (4): 1373-1393
- Szendroedi J, Sandtner W, Zarrabi T, Zebedin E, Hilber K, Dudley SC Jr, Fozzard HA, Todt H. (2007) Speeding the recovery from ultraslow inactivation of voltage-gated Na+ channels by metal ion binding to the selectivity filter: a foot-on-the-door? Biophys. J, 93(12): 4209-4224
- Sandtner W, Szendroedi J, Zarrabi T, Zebedin E, Hilber K, Glaaser I, Fozzard HA, Dudley SC, Todt H. (2004) Lidocaine: a foot in the door of the inner vestibule prevents ultra-slow inactivation of a voltage-gated sodium channel. Mol Pharmacol, 66(3): 648-657
- Mörtl D, Agneter E, Krivanek P, Koppatz K, Todt H. (2003) Dual rate-dependent cardiac electrophysiologic effects of haloperidol: slowing of intraventricular conduction and lengthening of repolarization. J. Cardiovasc. Pharmacol., 41(6): 870-9