A Proton Pore in the K Channel Voltage Sensor

Abstract

Several models have been proposed for how the movement of the voltage-sensing S4 domain of K channels from the "in" conformation to the "out" conformation (in and out refer to the position of the S4 domain relative to the membrane) results in channel opening. The S5 and S6 domains of each of the four subunits that form a functional channel contribute to the ion-selective pore of the channel. Starace and Bezanilla demonstrate that mutation of a specific arginine residue in the S4 domain of the Aeropyrum pernix K channel results in the formation of a proton pore. They replaced the first arginine in the S4 domain with histidine (R362H) and used electrophysiological recordings of oocytes expressing this mutated channel to determine that the channel can conduct K + ions through the channel pore and protons through the voltage sensor region. The R362H channel only conducted protons when the S4 domain was in the "in" conformation. Proton flux persisted if the pore for K + flux was blocked with agitoxin, thus suggesting that protons were flowing through the sensor region and not the K + pore. Blaustein and Miller discuss the implications for these results in understanding channel gating and refining the various proposed models. D. M. Starace, F. Bezanilla, A proton pore in a potassium channel voltage sensor reveals a focused electric field. Nature 427 , 548-553 (2004). [Online Journal] R. O. Blaustein, C. Miller, Shake, rattle or roll? Nature 427 , 499-500 (2004). [Online Journal]