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 |
|---|---|
| Pages (from-to) | 573-583 |
| Number of pages | 11 |
| Journal | Neuron |
| Volume | 27 |
| Issue number | 3 |
| State | Published - Dec 7 2000 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
A conserved glutamate is important for slow inactivation in K+ channels. / Larsson, Hans P; Elinder, Fredrik.
In: Neuron, Vol. 27, No. 3, 07.12.2000, p. 573-583.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A conserved glutamate is important for slow inactivation in K+ channels
AU - Larsson, Hans P
AU - Elinder, Fredrik
PY - 2000/12/7
Y1 - 2000/12/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033681165&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033681165&partnerID=8YFLogxK
M3 - Article
C2 - 11055439
AN - SCOPUS:0033681165
VL - 27
SP - 573
EP - 583
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 3
ER -