TY - JOUR AU - Li Ping AU - Sun Hai-feng AU - Zhou Ping-zheng AU - Ma Chao-ying AU - Hu Guo-yuan AU - Jiang Hua-liang AU - Li Min AU - Liu Hong AU - Gao Zhao-bing PY - 2016 TI - Comparison of the effects of DC031050, a class III antiarrhythmic agent, on hERG channel and three neuronal potassium channels JF - Acta Pharmacologica Sinica; Vol 33, No 6 (June 2012): Acta Pharmacologica Sinica Y2 - 2016 KW - N2 - Aim: This study was conducted to test the selectivity of DC031050 on cardiac and neuronal potassium channels. Methods: Human ether-à-go-go related gene (hERG), KCNQ and Kv1.2 channels were expressed in CHO cells. The delayed rectifier potassium current ( I K ) was recorded from dissociated hippocampal pyramidal neurons of neonatal rats. Whole-cell voltage patch clamp was used to record the voltage-activated potassium currents. Drug-containing solution was delivered using a RSC-100 Rapid Solution Changer. Results: Both DC031050 and dofetilide potently inhibited hERG currents with IC 50 values of 2.3±1.0 and 17.9±1.2 nmol/L, respectively. DC031050 inhibited the I K current with an IC 50 value of 2.7±1.5 μmol/L, which was >1000 times the concentration required to inhibit hERG current. DC031050 at 3 μmol/L did not significantly affect the voltage-dependence of the steady activation, steady inactivation of I K , or the rate of I K from inactivation. Intracellular application of DC031050 (5 μmol/L) was insufficient to inhibit I K . DC031050 up to 10 μmol/L had no effects on KCNQ2 and Kv1.2 channel currents. Conclusion: DC031050 is a highly selective hERG potassium channel blocker with a substantial safety margin of activity over neuronal potassium channels, thus holds significant potential for therapeutic application as a class III antiarrhythmic agent. UR - http://www.chinaphar.com/article/view/5633