Session: 5

PS5-12 | Neurotrophic factors regulate TREK2 expression in nociceptive DRG neurons

Diego Nicolás Messina

Laboratorio de Neurobiología del Dolor, IHEM - CONICET FCM UNCuyo

TREK2 is a member of the 2-pore domain family of K+ channels (K2P) preferentially expressed by unmyelinated, slow-conducting and non-peptidergic isolectin B4-binding (IB4+) primary sensory neurons of the dorsal root ganglia (DRG). TREK2 controls the resting membrane potential (Em) of these neurons affecting their excitability. We showed that there is a re-distribution of TREK2 away from the cell membrane, resulting in a more depolarised Em, 7 days after spinal nerve axotomy (SNA) of the L5 DRG. IB4+ neurons depend on the glial-derived neurotrophic factor (GDNF) family of ligands to maintain their phenotype. In the SNA model, neurons are deprived of peripherally-derived trophic factors. Thus we hypothesized that they might control the expression of TREK2. Using a combination of immunohistochemistry, immunocytochemistry and western blotting we tested whether the members of the GDNF-family (GDNF, neurturin and artemin) and their receptors (GFRα1, α2 and α3) were involved in controlling the expression of TREK2 in the DRG. We found that TREK2 correlated strongly with the 3 receptors normally and that this correlation changed ipsilaterally for GFRα1 and GFRα2 and contralaterally for GFRα3 in the SNA model. Moreover, only GDNF restored IB4-binding and a normal expression pattern of TREK2 in cultured DRG neurons. This is the first demonstration that GDNF controls the expression of a K2P channel in nociceptors, a finding with therapeutic potential in the treatment of chronic pain.