Journal article
Tetraethylammonium Block of the BNC1 Channel
Biophysical journal, Vol.76(3), pp.1377-1383
1999
DOI: 10.1016/S0006-3495(99)77299-1
PMCID: PMC1300116
PMID: 10049320
Abstract
The brain Na
+ channel-1 (BNC1, also known as MDEG1 or ASIC2) is a member of the DEG/ENaC cation channel family. Mutation of a specific residue (Gly430) that lies N-terminal to the second membrane-spanning domain activates BNC1 and converts it from a Na
+-selective channel to one permeable to both Na
+ and K
+. Because all K
+ channels are blocked by tetraethylammonium (TEA), we asked if TEA would inhibit BNC1 with a mutation at residue 430. External TEA blocked BNC1 when residue 430 was a Val or a Thr. Block was steeply voltage-dependent and was reduced when current was outward, suggesting multi-ion block within the channel pore. Block was dependent on the size of the quaternary ammonium; the smaller tetramethylammonium blocked with similar properties, whereas the larger tetrapropylammonium had little effect. When residue 430 was Phe, the effects of tetramethylammonium and tetrapropylammonium were not altered. In contrast, block by TEA was much less voltage-dependent, suggesting that the Phe mutation introduced a new TEA binding site located ∼30% of the way across the electric field. These results provide insight into the structure and function of BNC1 and suggest that TEA may be a useful tool to probe function of this channel family.
Details
- Title: Subtitle
- Tetraethylammonium Block of the BNC1 Channel
- Creators
- Christopher M AdamsMargaret P PricePeter M SnyderMichael J Welsh
- Resource Type
- Journal article
- Publication Details
- Biophysical journal, Vol.76(3), pp.1377-1383
- Publisher
- Elsevier Inc
- DOI
- 10.1016/S0006-3495(99)77299-1
- PMID
- 10049320
- PMCID
- PMC1300116
- ISSN
- 0006-3495
- eISSN
- 1542-0086
- Language
- English
- Date published
- 1999
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Cardiovascular Medicine; Neurosurgery; Medicine Administration; Internal Medicine
- Record Identifier
- 9984020795902771
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