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Identification of Specific Sensory Neuron Populations for Study of Expressed Ion Channels
Published on: December 24, 2013
WIN 17317-3, a new high-affinity probe for voltage-gated sodium channels
S G Wanner1, H Glossmann, H G Knaus
1Institute of Pharmacology, University of Innsbruck, Austria.
Biochemistry
|August 25, 1999
Summary
The iminodihydroquinoline WIN 17317-3, initially thought to target potassium channels, was found to be a potent blocker of sodium channels. This new high-affinity ligand selectively inhibits brain IIA sodium channels, offering a valuable tool for neuroscience research.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- The voltage-gated potassium channels K(v)1.3 and K(v)1.4 are inhibited by iminodihydroquinoline WIN 17317-3.
- These potassium channels are present in the brain, prompting the synthesis of radiolabeled WIN 17317-3 to study neuronal channels.
Purpose of the Study:
- To investigate the binding and functional effects of WIN 17317-3 in the brain.
- To determine if WIN 17317-3 interacts with neuronal potassium channels or other targets.
Main Methods:
- Synthesis of radiolabeled [(3)H]WIN 17317-3.
- Binding assays using rat brain synaptic membranes.
- Competition studies with known potassium and sodium channel ligands.
- Autoradiography of rat brain sections.
- Electrophysiological studies and sodium uptake assays in CHO cells expressing rat brain IIA sodium channels.
Main Results:
- [(3)H]WIN 17317-3 binds with high affinity (K(d) 2.2 nM) to a single site in rat brain membranes.
- Binding is modulated by sodium channel effectors, not potassium channel ligands.
- WIN 17317-3 distribution in rat brain aligns with sodium channel localization.
- WIN 17317-3 potently inhibits sodium currents (K(i) 9 nM) and sodium uptake in cells expressing brain IIA sodium channels.
- It shows subtype selectivity, affecting skeletal muscle sodium channels but less so cardiac channels.
Conclusions:
- WIN 17317-3 is a novel, high-affinity, subtype-selective ligand for sodium channels.
- It acts as a potent blocker of brain IIA sodium channels.
- WIN 17317-3 is a valuable pharmacological tool for studying sodium channel function in the brain.
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