High-throughput compound screening of Kv7.2/7.3 using the Automated Patch Clamp platform Qube 384

The heteromeric potassium channel KCNQ2 (K_V7.2)/KCNQ3 (K_V7.3) contributes to the subthreshold M-current in many neurons, helping regulate excitability and stabilize the membrane potential near rest. Upon hK_V7.2/7.3 channel opening, the excitability of neurons is decreased. Loss-of-function mutations have been found to underlie a spectrum of neurological diseases such as neonatal-onset epilepsy, and epileptic encephalopathy (Biervert et al., 1998; Jentsch, 2000; Maljevic et al., 2008; Weckhuysen et al., 2012; Kato et al., 2013), which makes the channel an interesting drug target.

In 2011, the hK_V7.2/7.3 channel opener retigabine was approved as an antiepileptic drug. Due to its adverse effects and lack of specificity, like activation of the hK_V7.4 channel, it was withdrawn from the market. However, retigabine validated opening of the hK_V7.2/7.3 channel as an antiepileptic strategy and thereby further put a spotlight on the development of drugs aiming at this channel.