Activation of neuronal Kv7/KCNQ/M-channels by the opener QO58-lysine and its anti-nociceptive effects on inflammatory pain in rodents.

ABSTRACT:

Aim

The aim of this study was to examine the activation of neuronal Kv7/KCNQ channels by a novel modified Kv7 opener QO58-lysine and to test the anti-nociceptive effects of QO58-lysine on inflammatory pain in rodent models.

Methods

Assays including whole-cell patch clamp recordings, HPLC, and in vivo pain behavioral evaluations were employed.

Results

QO58-lysine caused instant activation of Kv7.2/7.3 currents, and increasing the dose of QO58-lysine resulted in a dose-dependent activation of Kv7.2/Kv7.3 currents with an EC50 of 1.2±0.2 μmol/L. QO58-lysine caused a leftward shift of the voltage-dependent activation of Kv7.2/Kv7.3 to a hyperpolarized potential at V1/2=-54.4±2.5 mV from V1/2=-26.0±0.6 mV. The half-life in plasma (t1/2) was derived as 2.9, 2.7, and 3.0 h f

SUBMITTER: Teng BC 

PROVIDER: S-EPMC4973381 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature