Inward rectifier potassium channels: Cloning, expression and structure-function studies

Armando A. Lagrutta, Chris T. Bond, Xiao Ming Xia, Mauro Pessia, Stephen Tucker, John P. Adelman

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

A PCR-based cloning strategy was used to identify novel subunits of the two-transmembrane domain inward rectifier potassium channel family from rat brain, heart, and skeletal muscle. When expressed in Xenopus oocytes, two of these clones (Kir4.1 and Kir2.3) gave rise to inwardly rectifying potassium currents. Two-electrode voltage clamp commands to potentials negative to E(K) evoked inward potassium-selective currents which rapidly reached a peak amplitude and then relaxed to a steady-state level. Differences in the extent of current relaxation, the degree of rectification, and the voltage-dependent block by external cesium were detected. Two other members of this family (Kir5.1 and Kir3.4) did not produce macroscopic currents, when expressed by themselves, yet both subunits modified the currents when coexpressed with other specific members of the Kir family. Expression of chimeric subunits between Kir4.1 and either Kir5.1 or Kir3.4 suggested that the transmembrane domains determine the specificity of subunit heteropolymerization, while the C-terminal domains contribute to alterations in activation kinetics and rectification. Expression of covalently linked subunits demonstrated that the relative subunit positions, as well as stoichiometry, affect heteromeric channel activity.

Original languageEnglish (US)
Pages (from-to)651-660
Number of pages10
JournalJapanese Heart Journal
Volume37
Issue number5
DOIs
StatePublished - Sep 1996

Keywords

  • Heteromeric channel
  • Inward rectifier potassium channel (Kir)
  • Polymerase chain reaction (PCR)
  • Subunit positional effects
  • Two electrode voltage clamp (TEVC)
  • Two-transmembrane domain potassium channel family

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Lagrutta, A. A., Bond, C. T., Xia, X. M., Pessia, M., Tucker, S., & Adelman, J. P. (1996). Inward rectifier potassium channels: Cloning, expression and structure-function studies. Japanese Heart Journal, 37(5), 651-660. https://doi.org/10.1536/ihj.37.651