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The cytoplasmic half of S5 (5'S5) has been identified as part of the inner mouth of the pore based on evidence that mutations in this region greatly alter single channel conductance, 4-aminopyridine (4-AP) block and the rate of channel closing upon repolarization (deactivation). The latter effect, suggestive of a role for 5'S5 in channel gating was investigated in the present study. The biophysical properties of chimeric channels, in which the 5'S5 regions were exchanged between two host channels (Kv2.1 and Kv3.1) that differ in 4-AP sensitivity and deactivation rate, were examined in a Xenopus oocyte expression system. Exchange of 5'S5 between Kv2.1 and Kv3.1 confers steady-state voltage dependence of activation and rates of channel deactivation similar to those of the donor channel. The involvement of voltage-dependent gating was confirmed by the observation that exchanging the 5'S5 segment of Kv2.1 with that of Kv3.1 confers a change from slow to fast deactivation kinetics by accelerating the decay of off-gating charge movement. We suggest that a conformational change that extends from the voltage-sensor in S4 to the region of the pore lined by S5 regulates the stability of the open state. Therefore, the cytoplasmic end of S5, in addition to forming part of the conduction pathway near the inner mouth of the pore, also participates in the conformational rearrangements associated with late steps in channel activation and early steps in deactivation.
Key Words: potassium channels • gating • activation • deactivation • Xenopus oocyte
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