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Cited by 92Ion channel regulation and functionIon Transport and Channel RegulationCardiac electrophysiology and arrhythmias

Patterns of internal and external tetraethylammonium block in four homologous K+ channels.

Taglialatela, M, Vandongen, A M, Drewe, J A, Joho, R H, Brown, A M, Kirsch, G E·1991·Molecular Pharmacology
DOI 10.1016/s0026-895x(25)12953-2
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Abstract

Tetraethylammonium (TEA) is a small ion that is thought to block open K+ channels by binding either to an internal or to an external site. For this reason, it has been used to probe the ion conduction pathway or pore of K+ channel mutants and a K+ channel chimera. The results suggested that the region between transmembrane segments 5 and 6 (S5-S6 linker) was involved in the formation of both the internal and the external TEA binding sites and the K+ conduction pathway. Therefore, we compared internal and external TEA block of the currents expressed in Xenopus oocytes injected with RNAs from four related K+ channel clones, DRK1, RCK1, RCK2, and r-NGK2, which have only subtle structural differences in the S5-S6 linker. r-NGK2 was the most sensitive to external TEA and the least sensitive to internal TEA application. For DRK1 the profile was reversed. RCK1 was blocked equally well from either side, whereas RCK2 was more strongly blocked by internal TEA. The internal block was voltage dependent, whereas the external block was virtually voltage independent. As predicted from block of whole-oocyte currents, internal TEA produced a slow block of DRK1 and RCK2 single-channel currents but had almost no effect on r-NGK2 single-channel currents. Tetrapentylammonium produced a stronger block than TEA at the internal site, and the block was relieved by inward K+ currents, therefore suggesting that the internal TEA binding site is located within the K+ conduction pathway. These results, together with the TEA block of single-channel currents, establish what has until now been inferred by extrapolation from other studies, i.e., that TEA is an open-channel blocker in K+ channel clones. DRK1 mutants with extensive amino- and carboxyl-terminal deletions showed the same blocking profile as the parent DRK1. We conclude that TEA blocks these K+ channels at two sites, which define the inner and outer mouths of the channel pores. Comparison of the primary amino acid sequences in the S5-S6 linker suggests which residues may be responsible for the different patterns of TEA block.

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Authors
Taglialatela, M., Vandongen, A. M., Drewe, J. A., Joho, R. H., Brown, A. M., & Kirsch, G. E.
Affiliations
Baylor College of Medicine (US)
ORCID
Venue
Molecular Pharmacology
Publisher
Elsevier BV
Published
1991-08
Volume
40
Issue
2
Pages
299-307
ISSN
0026-895X (ISSN-L)
DOI
10.1016/s0026-895x(25)12953-2
OpenAlex
W1782707686
Cited by
92
References
27
Citations by year
2026: 3 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 2 · 2014: 1 · 2013: 4
FWCI
3.67
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Molecular Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca - Università degli Studi del Molise (submittedVersion)
  • PubMed
Funders
  • National Institutes of Health (5r01ns028407-09)
  • National Heart, Lung, and Blood Institute (R01HL036930, HL 36930)
  • National Institute of Neurological Disorders and Stroke (NS-28407, NS 23877, R01NS023877)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Keywords
tetraethylammonium, potassium channel blockade, tetrapentylammonium, single-channel currents, voltage dependence of block
MeSH terms
Quaternary Ammonium Compounds, Animals, Binding Sites, Metabolic Clearance Rate, Mutation, Structure-Activity Relationship, Tetraethylammonium Compounds, Potassium Channels, Rats

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