POTASSIUM CHANNEL BLOCKERS INHIBIT ADOPTIVE TRANSFER OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS BY MYELIN-BASIC-PROTEIN-STIMULATED RAT T-LYMPHOCYTES

Agents which block T cell K+ currents can prohibit both proliferative and effector cell functions in T cells activated by mitogens or phorbo l esters. This study examined the effects of some of these blocking ag ents on the immune responsiveness of guinea pig myelin basic protein ( GPMBP)-reactive Lewis rat T lymphocytes, which are capable of mediatin g the adoptive transfer of experimental allergic encephalomyelitis (EA E), an accepted animal model for multiple sclerosis. Both the prolifer ative functions (DNA synthesis and cell blastogenesis) and the EAE tra nsfer activities of GPMBP-reactive lymphocytes were examined following GPMBP-induced activation in the presence of agents shown to block the outwardly rectifying K+ current in these cells. At concentrations whi ch completely inhibited DNA synthesis, as measured by [H-3]thymidine i ncorporation, and cell blastogenesis, tetraethylammonium (TEA), 4-amin opyridine (4-AP) and methoxyverapamil (D600) completely blocked the su bsequent adoptive transfer of EAE into naive syngeneic Lewis rats. The concentrations at which these blockers produced a 50% reduction in DN A synthesis were estimated to be 16, 1.6 and 32 mu M for TEA, 4-AP and D-600, respectively, which were roughly equivalent to the EC50 to blo ck the K+ current. Apamine, a potent Ca2+-activated K+ channel blocker ? at a concentration several orders of magnitude higher than is necess ary to block Ca2+-activated K+ channels, reduced the maximal K+ conduc tance in GPMBP-reactive T cell K+ channels by about 20%, but did not a lter either [H-3]thymidine incorporation or the adoptive transfer of E AE. These results indicate that delayed rectifier K+ channel blockers may prevent the activation of GPMBP-reactive T cells, thus prohibiting encephalitogenic effector cell functions.