Recent evidence from proteomic research on ion channels indicates that these integral membrane proteins do not operate as 'stand-alone-tools', but are rather assembled into larger protein complexes (supercomplexes or microdomains) which, based on protein-protein interactions, determine specificity, speed and regulation of ion channel-mediated signal transduction.

Using affinity-purification and nanoflow liquid-chromatography tandem mass spectrometry (nano-LC-MS/MS) on plasma membrane fractions we investigated the protein complexes of the calcium-activated BKCa and SKCa potassium channels as well as the voltage-gated Kv1.1 channels. In either case biochemical analyses identified a number of proteins that are directly or indirectly associated with the pore-forming subunits of these ion channels. Functional analyses on heterologously reconstituted multi-protein complexes showed that the identified partner molecules control the channels' gating characteristics as well as their processing and/or subcellular localization.

In addition, we analysed the phosphorylation status of the purified channel alpha subunits in order to understand the molecular nature of their dynamic regulation.