Sussex Neuroscience

Dr Ruth Murrell-Lagnado

RML

A Voltage-gated Potassium Channel as a Drug Target in the treatment of Neuropathic Pain

Ruth Murrell-Lagnado. Sussex Neuroscience and Sussex Drug Discovery Centre

A key driver of neuropathic pain is spontaneous activity in damaged sensory neurons, occurring as a result of disease or injury. There is an urgent need for new therapies to treat this type of chronic pain, hence the need to validate potential new drug targets which can regulate the firing properties of these sensory neurons. One such target is Kv9.1, which belongs to the voltage-gated potassium channel family. In mouse models of neuropathic pain, the downregulation of Kv9.1 has been shown to occur in sensory neurons following nerve injury, enhancing neuronal excitability and triggering pain behaviors1. In the Sussex Drug Discovery Centre (SDDC) we are developing patch clamp and flux assays to help identify new ligands which potentiate the activity of Kv2.1/Kv9.1 heteromeric potassium channels. Kv9.1 is a silent subunit which cannot form an ion channel alone, but partners with Kv2.1 to make a functioning channel. This project will examine the properties of Kv2.1/9.1 heteromeric assemblies both in terms of their electrophysiological properties and also their ability to form clusters that stabilize signalling platforms between the plasma membrane and the endoplasmic reticulum. The student will join a team based in SDDC and Sussex Neuroscience, that are generating cell lines with varied ratios of Kv2.1 : Kv9.1 expression. The project will involve cell culture, fluorescence microscopy imaging and patch clamp.

Selected publications

(For full list of publications and more details about the lab, please visit: http://www.sussex.ac.uk/lifesci/murrelllagnadolab)

1. Tsantoulas et al., (2012) Sensory Neuron Downregulation of the Kv9.1 Potassium Channel Subunit Mediates Neuropathic Pain following Nerve Injury. Journal of Neuroscience, 32 (48) 17502-17513