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 phorbol esters. This study examined the effects of some of these blocking agents on the immune responsiveness of guinea pig myelin basic protein (GPMBP)-reactive Lewis rat T lymphocytes, which are capable of mediating the adoptive transfer of experimental allergic encephalomyelitis (EAE), an accepted animal model for multiple sclerosis. Both the proliferative functions (DNA synthesis and cell blastogenesis) and the EAE transfer 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 which completely inhibited DNA synthesis, as measured by [(3)H]thymidine incorporation, and cell blastogenesis, tetraethylammonium (TEA), 4-aminopyridine (4-AP) and methoxyverapamil (D60) completely blocked the subsequent adoptive transfer of EAE into naive syngeneic Lewis rats. The concentrations at which these blockers produced a 50% reduction in DNA synthesis were estimated to be 16, 1.6 and 32 &mgr;M for TEA, 4-AP and D-600, respectively, which were roughly equivalent to the EC(50) to block the K(+) current. Apamine, a potent Ca(2+)-activated K(+) channel blocker, at a concentration several orders of magnitude higher than is necessary to block Ca(2+)-activated K(+) channels, reduced the maximal K(+) conductance in GPMBP-reactive T cell K(+) channels by about 20%, but did not alter either [H(3)H]thymidine incorporation or the adoptive transfer of EAE. These results indicate that delayed rectifier K(+) channel blockers may prevent the activation of GPMBP-reactive T cells, thus prohibiting encephalitogenic effector cell functions. Copyright 1997 S. Karger AG, Basel
Judge
S.I.V.
SI
Interdepartmental Graduate Neuroscience Program, Northwestern University, Evanston, Ill., USA.
Yeh
J.Z.
JZ
Mannie
M.D.
MD
Pope Seifert
L.
L
Paterson
P.Y.
PY