FOR 1086:  K2P-Channels - From Molecules to Physiology and Pathophysiology

• Subject Area: Medicine
• Term: from 2008 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 66618578

Two-pore-domain potassium channels (K2P-channels) represent the most recently discovered class of potassium channels. The family of K2P-channels in humans comprises 15 members. The name of the channels was derived from their structure: Every subunit possesses two pore domains and four transmembrane domains. Functional K2P-channels assemble as dimers, in which altogether four pore domains form a potassium-selective pore (all other potassium channels possess only one pore domain per subunit and assemble as tetramers). The activity of K2P channels is regulated in a very complex manner, for example by neurotransmitters, by local pH changes, polyunsaturated fatty acids, mechanical stretch of the membrane, heat and inhalation anaesthetics. K2P-channels are potentially interesting drug targets and could open up new strategies for the treatment of various diseases. The pathophysiologically interesting processes in which K2P-channels are involved include neuroprotection, inhalation anaesthesia, nociception, epilepsy, cardiac arrhythmias, renal disturbances of salt- and water balance, pulmonary hypertension, cell proliferation and endocrine disorders.
The aim of the Research Unit is to unite the research groups working in Germany in the field of K2P-channels to a joint project: the elucidation of the physiology and pathophysiology of K2P-channels and the development of new therapeutic strategies with K2P-channels as drug targets.
The Research Unit aims to
(1) contribute to a better understanding of the function of K2P-channels in various organs,
(2) characterise specific inhibitors of K2P-channels and construct transgenic mice and other disease models,
(3) construct a pore homology model to facilitate the rational design of new channel blockers,
(4) promote the translation of basic research to the development of novel therapeutic options and
(5) improve the training of young scientists by allowing them to participate in the joint projects of the participating research groups.

• DFG Programme: Research Units
• International Connection: Denmark

Projects

• Bedeutung von TASK-Kanälen für die Funktion der Nebennierenrinde und für die Regulation der Atmung (Applicant Warth, Richard )
• Die Mechanismen der rezeptorabhängigen Regulation von TASK- und TREK-Kanälen. (Applicant Oliver, Dominik )
• Funktion und Signaltransduktion von TASK-1 und TREK-1 Kanälen im Herz-Kreislauf-System. (Applicant Daut, Jürgen )
• Genetische Variation in kardialen K2P-Kanalgenen und Arrhythmieformen (Applicant Schulze-Bahr, Eric )
• K2P-Kanäle - vom Molekül zur Physiologie und Pathophysiologie (Applicant Daut, Jürgen )
• Mechanismen der Regulation des intrazellulären Transports von TASK-1 und TASK-3 (Applicant Schwappach-Pignataro, Blanche )
• Mechanistisch/strukturelle Aufklärung der Regulationsmechanismen in K2P-Kanälen (Applicant Baukrowitz, Thomas )
• Modulation, Funktion und neuroprotektives Potential von TASK- und TRESK-Kanälen im zentralen Nervensystem (Applicants Budde, Thomas ;  Meuth, Sven G. )
• Physiologische und pathophysiologische Bedeutung vaskulärer K²P-Kanäle (Applicant Köhler, Ralf )
• TASK Kanäle im Herzen und deren extrazelluläre Poren-Struktur (Applicant Decher, Ph.D., Niels )

• Spokesperson: Professor Dr. Jürgen Daut