Investigating the role of Kv1.6 in pain pathways (360G-Wellcome-109117_Z_15_A)

Kv1.6 is a member of the Shaker-like Kv1 potassium channel protein family. Widely expressed in the nervous system, these channels have delayed outward rectifier properties and evidence indicates that they act to suppress action potential firing. In the field of neuropathic pain, of which neuronal hyperexcitabilty is a common hallmark, these channels are of interest as their malfunction or downregulation may contribute to the disease pathophysiology. While less is known of Kv1.6 than other subunits of the same family, it has recently been reported that this channel is upregulated following nerve injury, signifying some role for Kv1.6 during the time after injury. Pharmacological inhibition at this stage indicates a functional role for Kv1.6 in restoring hypersensitive pain thresholds somewhat towards more normal values. Having already conducted some preliminary research on the Kv1.6 knock-out mouse, I will employ various in vivo, ex vivo and in vitro techniques from behavioural chronic pain models to electrophysiology, calcium signalling and gene/protein expression analysis in order to further probe the importance of this channel in health and disease, and to determine its sites of action amongst the various neuronal populations along somatosensory/pain pathways in the peripheral and/or central nervous system.