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 disulfidelinking 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.
Original language | English (US) |
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Pages (from-to) | 573-583 |
Number of pages | 11 |
Journal | Neuron |
Volume | 27 |
Issue number | 3 |
DOIs | |
State | Published - 2000 |
Externally published | Yes |
ASJC Scopus subject areas
- Neuroscience(all)