CORTEX Conference by Thomas Boulin

The central goal of our group is to understand the molecular and cellular mechanisms that control the excitability of neurons and muscles. We are particularly interested in processes that involve two-pore domain (K2P) potassium channels. We combine genetic strategies in the model nematode C. elegans (including state-of-the art genome engineering) with electrophysiology in heterologous expression systems (Xenopus oocytes) to understand how cells control the number, the activity, and the distribution of ion channels at their surface.

 

K2P potassium channels form a large family of well-conserved ion channels that play a central role in the establishment and maintenance of the resting membrane potential of almost all animal cells. In the vertebrate nervous system, various neuromodulators promote K2P closure and therefore increase neuronal excitability. Modulation of K2P channel activity has been linked to physiopathological processes such as sleep, epilepsy, depression, and pain perception. K2Ps are major targets of volatile general anaesthetics, mediating immobilization and sedation. Recently, mutations in K2P channels have been implicated in rare human diseases affecting the function of the nervous system (Birk Barel mental retardation with dysmorphism syndrome, FHEIG neuro-developmental disorder).

 

Despite the basic function of these channels, comparatively little is known about factors that specifically regulate the expression, the activity, and the localization of K2P channels at the cell surface. We have successfully used unbiased forward genetic screening methods to reveal novel and unsuspected links between nematode K2P channels and major cellular actors such as Ankyrin, Spectrin, Notch, and Dystrophin.