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- Larsson, HP, et al.
(författare)
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A conserved glutamate is important for slow inactivation in K+ channels
- 2000
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Ingår i: Neuron. - : Elsevier Science B.V., Amsterdam.. - 0896-6273 .- 1097-4199. ; 27:3, s. 573-583
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Tidskriftsartikel (refereegranskat)abstract
- Voltage-gated ion channels undergo slow inactivation during prolonged depolarizations. We investigated the role of a conserved glutamate at the extracellular end of segment 5 (S5) in slow inactivation by mutating it to a cysteine (E418C in Shaker). We could lock the channel in two different conformations by disulfide-linking 418C to two different cysteines, introduced in the Pore-S6 (P-S6) loop. Our results suggest that E418 is normally stabilizing the open conformation of the slow inactivation gate by forming hydrogen bonds with the P-S6 loop. Breaking these bonds allows the P-S6 loop to rotate, which closes the slow inactivation gate. Our results also suggest a mechanism of how the movement of the voltage sensor can induce slow inactivation by destabilizing these bonds.
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| 2. |
- Broomand, Amir, et al.
(författare)
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Large-Scale Movement within the Voltage-Sensor Paddle of a Potassium Channel-Support for a Helical-Screw Motion
- 2008
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 59:5, s. 770-777
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Tidskriftsartikel (refereegranskat)abstract
- The size of the movement and the molecular identity of the moving parts of the voltage sensor of a voltage-gated ion channel are debated. In the helical-screw model, the positively charged fourth transmembrane segment S4 slides and rotates along negative counter charges in S2 and S3, while in the paddle model, S4 carries the extracellular part of S3 (S3b) as a cargo. Here, we show that S4 slides 16-26 Å along S3b. We introduced pairs of cysteines in S4 and S3b of the Shaker K channel to make disulfide bonds. Residue 325 in S3b makes close and state-dependent contacts with a long stretch of residues in S4. A disulfide bond between 325 and 360 was formed in the closed state, while a bond between 325 and 366 was formed in the open state. These data are not compatible with the voltage-sensor paddle model, but support the helical-screw model. © 2008 Elsevier Inc. All rights reserved.
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