CONTRIBUTION OF THE S4 SEGMENT TO GATING CHARGE IN THE SHAKER K+ CHANNEL

Voltage-activated ion channels respond to changes in membrane voltage by coupling the movement of charges to channel opening. A K+ channel-s pecific radioligand was designed and used to determine the origin of t hese gating charges in the Shaker K+ channel. Opening of a Shaker K+ c hannel is associated with a displacement of 13.6 electron charge units . Gating charge contributions were determined for six of the seven pos itive charges in the S4 segment, an unusual amino acid sequence in vol tage-activated cation channels consisting of repeating basic residues at every third position. Charge-neutralizing mutations of the first fo ur positive charges led to large decreases (similar to 4 electron char ge units each) in the gating charge; however, the gating charge of Sha ker Delta 10, a Shaker K+ channel with 10 altered nonbasic residues in its S4 segment, was found to be identical to the wild-type channel. T hese findings show that movement of the NH2-terminal half but not the CO2H-terminal end of the S4 segment underlies gating charge, and that this portion of the S4 segment appears to move across the entire trans membrane voltage difference in association with channel activation.