Modulation of Outward K(+) Conductance Is a Post-Activational Event in Rat T Lymphocytes Responsible for the Adoptive Transfer of Experimental Allergic Encephalomyelitis.

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