A Study On The Effect Mechanism And Binding Sites Of Ephedrine To KCNQ1/KCNE1 Channel

Ion channels are pore proteins of cellular membrane and the ion flow is the basis of signal transferring among different cells. Potassium channel is a popular branch of membrane protein which plays very important roles in many physiological activities. KCNQ gene is a family of the genes encoding voltage-dependent potassium channels. KCNQ1(KV7.1)α-subunits and KCNE1β-subunit co-assemble to form channels that conduct the slow delayed rectifier K+ current(IKs)in the heart.Ephedrine which is similar to the adrenaline is a main component of the traditional Chinese medicine Mahuang, and pseudoephedrine is ephedrine optically active isomer. When ephedrine works on the heart, the blood pressure rises, the coronary vessels expands, and the myocardial contractile force strengthens so the heart can pump more blood without the heart rate changing much.KCNQ1/KCNE1 channels were heterologously expressed in Xenopus laevis oocytes and currents were recorded using the two-microelectrode voltage-clamp technique. Eliminating the interfere of KCNE1 channels and the native channels in the ooxytes, 1μM Ephedrine increased the KCNQ1/KCNE1 currents amplitude, at +40mV. Besides, the activation occurred rapidly, with a steady level achieved in 2 minutes after the replacement of bath solution. Our study explains that how ephedrine works on the heart and the mechanism of the sudden death due to the side reaction of ephedrine.The two residues, F296 and Y299, located near the pore helix of KCNQ1, are considered the bind site of the ephedrine. When F296 and Y299 are mutated to V, ephedrine had no effects on these mutated channels. The benzene rings of 296 and 296 interact with the benzene ring of ephedrine, and make the ions flow the ion channels more facilely.