Functional channel formation associated with cytotoxic T-cell granules

J. D.E. Young, C. F. Nathan, E. R. Podack, M. A. Palladino, Z. A. Cohn

Research output: Contribution to journalJournal Article peer-review

81 Scopus citations

Abstract

Lymphocyte granules from cytotoxic T-lymphocyte lines A2, A11, and R8 were enriched by subcellular fractionation using a Percoll gradient. Granule-enriched fractions showed potent hemolytic activity in the presence of Ca2+. Isolated granules induced rapid Ca2+-dependent membrane depolarization of J774 macrophage-like cells. When tested in planar bilayers, granules induced the formation of Ca2+-dependent functional ion channels of large conductance steps of 1-6 nS in 0.1 M NaCl. Granule-induced channels were resistant to closing by an increase in transmembrane potential, with few channels shifting to the closed state only at voltages of >70 mV, following a Poisson process. These channels showed poor ion selectivity and were permeable to all monovalent and divalent ions (K+, Na+, Li+, Cl-, Ca2+, Mg2+, Zn2+, Ba2+). Ultrastructural examination of soluble granule proteins incubated for 48 hr at 37° C in the presence of Ca2+ revealed ring-like structures of 150-200 Å. Structural and functional channel formation may be involved in cytolysis induced by cytotoxic T lymphocytes.

Original languageEnglish
Pages (from-to)150-154
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume83
Issue number1
DOIs
StatePublished - 1986
Externally publishedYes

Keywords

  • Animals
  • Calcium
  • Cell Fractionation
  • Cell Line
  • Cell Membrane
  • Cell Membrane Permeability
  • Cytoplasmic Granules
  • Electric Conductivity
  • Erythrocytes
  • Hemolysis
  • Ion Channels
  • Ions
  • Lipid Bilayers
  • Macrophages
  • Membrane Lipids
  • Membrane Potentials
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Cytotoxic

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