- 作者: Susan I.V. Judge; Philip Y. Paterson; Mark D. Mannie; Jay Z. Yeh
- 作者服務機構: a Interdepartmental Graduate Neuroscience Program, Northwestern University, Evanston, Ill., Departments of ; b Molecular Pharmacology and Biological Chemistry and ; c Microbiology-Immunology, Northwestern University Medical School, Chicago, Ill.,USA
- 中文摘要: --
- 英文摘要: 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 GP 1 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.
- 中文關鍵字: --
- 英文關鍵字: Potassium channel; Ion channels; Lymphocytes; Allergic encephalomyelitis; Encephalitogenic basic protein; Lymphocyte transformation