Subthreshold ion channels in epileptogenesis and neuronal synchronization

Coordinator:    Prof. Dr. Dirk Isbrandt
Institution: University of Hamburg
The main goal of our project is to understand the mechanisms of epileptogenesis and neu-ronal synchronization in hyperexcitable neuronal networks caused by dysfunctional ion channels. Our ultimate aim, which is at the core of EMINet, is to use the understanding of epileptogenesis gained from our animal models to develop new strategies for the prevention and cure of epilepsy.
We are using a multidisciplinary approach that combines several tools of methodology and analysis, such as the generation and molecular biological characterization of mouse mutants with selectively altered ion channel activities as well as an in-depth behavioral and in vivo electrophysiological characterization using multi-electrode single-cell recordings in freely moving mice. The use of cutting-edge technology allows us to gain access to data that, for technical reasons, cannot be obtained from patients. These results are likely to provide information on epilepsy surrogate markers in order to form the theoretical basis for future diagnosis and treatment. We specifially study Kv7 (KCNQ/M), Kv4 (A-type), and HCN (H) ion channels, which control information processing in neurons. These ion channels are already active at membrane potentials negative to the action potential threshold (the so-called subthreshold membrane potential range), and may thus exert pivotal control over neuronal excitability and response patterns. Changes in the activities of these ion channels, either inherited, that is, caused by gene mutations, or acquired, that is, as a secondary result of another pathologic process (e.g., epileptic seizures or trauma), lead to profoundly altered biophysical properties of the affected neurons with far-reaching consequences for neuronal network activity and behavior.
The systematic study of these ion channels with the help of transgenic animal models within the framework of EMINet will greatly advance our knowledge of their physiological functions in the control of cellular and network excitability, information coding and cognition, and their roles in neurological diseases such as epilepsy.

Additional relevant Internet links:
Universitätsklinikum Hamburg-Eppendorf
Zentrum für Molekulare Neurobiologie Hamburg
Further Coordinators:
INTRANET (Members login)