TY  - GEN
N2  - Excitable cells use specific combinations of ion channels in order to set their electrical properties. The recent discovery of the two pore domain potassium channels (K2P) revealed the molecular substrates for resting K+ currents in neuronal cells. To date fifteen members of the K2P family, grouped into six distinct subfamilies (TWIK, THIK, TREK, TASK, TALK and TRESK) have been identified and characterized, some of them being highly expressed in the central and peripheral nervous system. K2P channels generate leak K+ currents which contribute to the resting membrane potential and play important roles in modulating neuronal excitability. K2P subunits can assemble as homodimers or heterodimers when coexpressed in neurons. There are no pharmacological agents that selectively block the K2P channel subtypes. Thus, it is difficult to dissect their contribution to the leak K+ background current. The TASK (TWIK-related acid-sensitive K+ channel) subfamily consists of TASK-1, TASK-3 and the non-functional TASK-5 channels. TASK-1 and TASK-3 channels are expressed in the brain, can sense physiologically relevant changes in extracellular pH and are modulated by neurotransmitters. In this thesis I analyzed the expression of TASK-1 and TASK-3 genes in the adult mouse brain. The TASK-1 gene has a restricted expression pattern, with highest level in cerebellar granule cells whereasTASK-3 gene has a strong expression in all brain regions. To understand the role of TASK-3 in the K+ leak conductance and in neuronal excitability I generated TASK-3 knockout mice and undertook some analysis of their phenotype. The K+ leak current of cerebellar granule cells was reduced to 50% and granule cells fired fewer action potentials in response to current injection. Despite these strong changes on the electrophysiological level, the motor behaviour of the TASK-3 knockout mice was unchanged, indicating possible compensatory mechanisms. The TASK-3 knockout mice will be useful for investigating: the contribution of TASK-3 channels to the leak currents in particular neuronal cell types (e.g. cerebellar granule cells, thalamic relay cells), the heteromeric assembly between TASK-1 and TASK-3 subunits in vivo, the involvement of TASK-3 channels in thalamocortical relay neurons in initiating arousal, their contribution to the anesthesia produced by inhalational anesthetics, their role in regulating apoptosis in developing cerebellar granule cells, their possible role in protection from brain ischemia, their contribution to homeostatic plasticity in cerebellar granule cells and their contribution to blood pressure regulation and blood oxygen sensing. 
AV  - public
A1  - Sandu, Cristina Gabriela
ID  - heidok7443
Y1  - 2006///
TI  - The generation and the characterization of the TASK-3 knockout mice
KW  - two-pore-domain potassium channel 
KW  -  TASK-3
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/7443/
ER  -