Effect of tyrphostin AG879 on Kv4.2 and Kv4.3 potassium channels

摘要: Background and Purpose A-type potassium channels (IA) are important proteins for modulating neuronal membrane excitability. The expression activity of Kv4.2 critical neurological functions pharmacological inhibitors may have therapeutic potential Fragile X syndrome. While screening various compounds, we identified tyrphostin AG879, a tyrosine kinase inhibitor, as inhibitor from. In the present study characterized effect AG879 on cloned Kv4.2/Kv channel-interacting protein 2 (KChIP2) channels. Experimental Approach To screen library pharmacologically active thallium flux assay was performed HEK-293 cells transiently-transfected with cDNA using Maxcyte transfection system. effects were further examined CHO-K1 expressing Kv4.2/KChIP2 whole-cell patch-clamp technique. Key Results Tyrphostin selectively dose-dependently inhibited Kv4.3 channels. channels, induced prominent acceleration inactivation rate, use-dependent block slowed recovery from inactivation. hyperpolarizing shift in voltage-dependence steady-state without apparent V1/2 voltage-dependent activation. blocking enhanced channel increased. Furthermore, significantly A-type currents cultured hippocampus neurons. Conclusion Implications AG879 selective potent channel. by preferentially interacting open state accelerating their