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 language | English (US) |
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Pages (from-to) | 98-110 |
Number of pages | 13 |
Journal | Journal of Biomedical Science |
Volume | 4 |
Issue number | 2-3 |
DOIs | |
State | Published - Mar 1997 |
Funding
This work was undertaken in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the field ofneurosci-ence at Northwestern University, Evanston, Ill., USA. This research was supported by Public Health Service Grant T32 NS07140.
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)