"Silent" voltage-gated K+ channel subunits – no simple silent bystanders: analysis of their pharmacological profile, physiological role and gating mechanism.

Voltage-gated K+ (Kv) channels play an important role in neuronal excitability which is reflected by several severe diseases caused by Kv channel dysfunction such as epilepsy. The Kv2 subfamily contains two members that display similar properties. The diversity is increased by assembly with members of the so-called silent Kv (KvS) subfamilies (Kv5-Kv6 and Kv8-Kv9). KvS subunits do not form functional homotetramers on their own but assemble into functional Kv2/KvS heterotetramers that display modified biophysical properties compared to Kv2.1 homotetramers. Further, diversity is increased by interactions with auxiliary ß-subunits. In addition, KvS subunits display a more tissue-specific expression compared to the ubiquitously expressed Kv2.1 creating tissue-specific functions for Kv2/KvS channels. Therefore, Kv2/KvS channels are more desirable pharmacological and therapeutic targets than Kv2 homotetramers. To fully understand Kv2.1/KvS channel complexes' pharmacological relevance as well as their role in neuronal physiology and diseases, it is important to unravel the molecular architecture of KvS containing channel complexes, to elucidate their role in neural excitability, to define how KvS subunits exert their unique effects and to determine the molecular determinants of channel opening and closing of these KvS containing channels. These are the topics of this "postdoctoral fellow renewal" application.

Keywords:VOLTAGE-GATED ION CHANNELS, MOLECULAR MECHANISMS

Disciplines:Biophysics

Project type:Collaboration project