Overview
- Peretz, A. et al. (2005) Mol. Pharmacol. 67, 1053.
Alomone Labs Diclofenac sodium salt enhances KCNQ2/KCNQ3 heteromeric channels expressed in Xenopus oocytes.A. Time course of KCNQ2/KCNQ3 current enhancement by 100, 200 and 500 µM Diclofenac sodium salt (#D-181). Currents were elicited by application of voltage step from a holding potential of -100 mV to -60 mV (800 msec). B. Superimposed example traces of current responses before and during perfusion of 100, 200 and 500 µM Diclofenac sodium salt, as indicated.
KV7 or KCNQs are voltage-gated potassium channels. These channels are mainly responsible for the cardiac and auditory IKs current and the neuronal M-current but can be found in other tissues as well. Voltage-gated potassium channels are tetramers of α-subunits, which surround a K+-selective pore1. The different five KCNQ subtypes have distinct assembly preferences encoded by a C-terminal cytoplasmic assembly domain, the A-domain Tail. This domain is a self-assembling, parallel, four-stranded coiled coil2.
Diclofenac (Voltaren) is a synthetic opener of KCNQ channels with an effective concentration of 1-500 μM. The opening mechanism by Diclofenac is not fully understood and it is hypothesized that this is achieved by either destabilizing the closed channel conformation or stabilizing the channel in its open state. Diclofenac reduces evoked and spontaneous action potentials in neuronal cells. In addition, it also enhances M-currents and to exhibit anti-convulsing properties thus making it a possible drug template for the treatment of neuronal hyper excitability pathologies such as epilepsy, migraine or neuropathic pain. Diclofenac is also a non-steroidal anti-inflammatory drug preventing inflammation via the non-selective inhibition of the enzymes COX1 and COX2 and the reduction of Prostaglandin production3.
