Modulation of outward K+ conductance is a post-activational event in rat T lymphocytes responsible for the adoptive transfer of experimental allergic encephalomyelitis

Susan I.V. Judge*, Philip Y. Paterson, Mark D. Mannie, Jay Z. Yeh

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Experimental allergic encephalomyelitis (EAE) is an accepted animal model for the human demyelinating disease multiple sclerosis. The continuously propagated line of Lewis rat T helper lymphocytes (GP1 T cells), specific for the encephalitogenic 68-86 sequence of guinea pig myelin basic protein (GPMBP), mediates the adoptive transfer of EAE into normal syngeneic Lewis rats. Because mitogenic activation of T cells can increase K+ conductance, this study investigated changes in the outwardly rectifying K+ conductance in GP1 T cells following activation with the encephalitogen, GPMBP. Using the gigohm-seal whole-cell variation of the patch clamp technique, GP1 T cells were studied during a 3-day culture with GPMBP and throughout the subsequent 10 days, as cells progressed through both GPMBP- induced activation (EAE transfer activity) and proliferation responses, finally reverting to the resting state. Resting GP1 T cells exhibited peak K+ conductances around 2 nS, while GPMBP-induced activation resulted in 5- to 10-fold increases in peak K+ conductance, which temporally coincided with the optimal period of EAE transfer activity. During and immediately after the optimal period for EAE transfer, 20-mV depolarizing shifts in the voltage dependence of both activation and inactivation developed, abruptly reversing to resting values as cells reverted to the resting state. Accompanying the depolarizing shifts were a slowing of the K+ current activation kinetics and an acceleration of the deactivation kinetics. These results indicate that the K+ conductance in GP1 rat T helper cells is modulated over the full time course of GPMBP-induced cellular responses and that K+ channels should be optimally available during the period of adoptive EAE transfer, preceding disease manifestation.

Original languageEnglish (US)
Pages (from-to)98-110
Number of pages13
JournalJournal of Biomedical Science
Volume4
Issue number2-3
DOIs
StatePublished - Mar 1 1997

Keywords

  • Allergic encephalomyelitis
  • Encephalitogenic basic protein
  • Ion channels
  • Lymphocyte transformation
  • Lymphocytes
  • Potassium channel

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

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