Ion currents through mutant phospholemman channel molecules

Zhen Hui Chen, Larry R. Jones, J. Randall Moorman

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Phospholemman (PLM), a small membrane protein with a single transmembrane domain, is a major substrate for protein kinases in muscle. In lipid bilayers, PLM forms ion channels with two unusual features - selectivity for the zwitterion taurine, and switching among cation- and anion-selective conformations. To investigate the molecular determinants of channel behavior, we measured ion currents through (1) PLM channels with point mutations in the extracellular and cytoplasmic domains, (2) chimeric PLM channels with the transmembrane domain of IsK, a K channel subunit, and (3) truncated PLM channels lacking the cytoplasmic domain. Truncated channels and those with a mutation at the cytoplasmic face had altered selectivity. Channels with a point mutation neat, the extracellular face were non-selective. Switching among channel conformations was less frequent in truncated channels and in channels with point mutations in either the extracellular or cytoplasmic domain. Chimeric channels with a different transmembrane domain had only a small reduction in conductance. We conclude that both the extracellular and cytoplasmic domains play roles in channel selectivity and conformational changes, Cation-binding sites appear to lie in the cytoplasmic domain, and an anion-binding site may reside in the extracellular domain. The cytoplasmic domain may function as a 'ball and chain' to regulate channel selectivity.

Original languageEnglish (US)
Pages (from-to)435-447
Number of pages13
JournalReceptors and Channels
Volume6
Issue number6
StatePublished - Dec 1 1999

Fingerprint

Ions
Molecules
Point Mutation
Anions
Conformations
Cations
Binding Sites
Lipid bilayers
Taurine
Lipid Bilayers
Ion Channels
Protein Kinases
Muscle
Membrane Proteins
phospholemman
Muscles
Mutation
Substrates

Keywords

  • Ion channels
  • Lipid bilayers
  • Membrane electrophysiology
  • Phosphorylation
  • Taurine

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Ion currents through mutant phospholemman channel molecules. / Chen, Zhen Hui; Jones, Larry R.; Moorman, J. Randall.

In: Receptors and Channels, Vol. 6, No. 6, 01.12.1999, p. 435-447.

Research output: Contribution to journalArticle

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