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 for 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. Copyright 1997 S. Karger AG, Basel
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