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Ligand-induced Closure of Inward Rectifier Kir6.2 Channels Traps Spermine in the Pore
- Source :
- The Journal of General Physiology
- Publication Year :
- 2003
- Publisher :
- Rockefeller University Press, 2003.
-
Abstract
- Small organic amines block open voltage-gated K+ channels and can be trapped by subsequent closure. Such studies provide strong evidence for voltage gating occurring at the intracellular end of the channel. We engineered the necessary properties (long block times with unblock kinetics comparable to, or slower than, the kinetics of gating) into spermine-blocked, ATP-gated (N160D,L157C) mutant KATP channels, in order to test the possibility of “blocker trapping” in ligand-gated Kir channels. Spermine block of these channels is very strongly voltage dependent, such that, at positive voltages, the off-rate of spermine is very low. A brief pulse to negative voltages rapidly relieves the block, but no such relief is observed in ATP-closed channels. The results are well fit by a simple kinetic model that assumes no spermine exit from closed channels. The results incontrovertibly demonstrate that spermine is trapped in channels that are closed by ATP, and implicate the M2 helix bundle crossing, or somewhere lower, as the probable location of the gate.
- Subjects :
- Helix bundle
spermine
Voltage-gated ion channel
Physiology
Inward-rectifier potassium ion channel
Stereochemistry
Chemistry
Kinetics
Spermine
Cardiac action potential
Gating
Kir6.2
Ligands
inward rectifier
Article
ATP
chemistry.chemical_compound
K channel
COS Cells
Chlorocebus aethiops
gating
Biophysics
Animals
Potassium Channels, Inwardly Rectifying
Ion Channel Gating
Subjects
Details
- ISSN :
- 15407748 and 00221295
- Volume :
- 122
- Database :
- OpenAIRE
- Journal :
- Journal of General Physiology
- Accession number :
- edsair.doi.dedup.....cc785739e4a010e1b1b452f50fc649ab
- Full Text :
- https://doi.org/10.1085/jgp.200308953