Dihydropyridine Bay K 8644 activates T lymphocyte calcium-permeable channels.
The effects of the dihydropyridine calcium channel agonist Bay K 8644 on indo-1-loaded Jurkat human leukemia T lymphocytes was assessed by flow cytometry. Bay K 8644 from 10(-9) to 10(-4) M caused a dose-dependent rise in the intracellular free Ca concentration, an effect that was not mimicked by the dihydropyridine Ca antagonist nifedipine. Single channel recordings by the extracellular patch-clamp technique indicated that Bay K 8644 activated an 8-pS, barium-permeable channel that opened as bursts of brief events. The channel appeared to be identical to the previously described voltage-insensitive, messenger-mediated, calcium-permeable channel involved in T cell activation. The predominant effect of Bay K 8644 on these channels was to increase the probability of channel reopening, apparently without a major effect on mean channel open-time. The results suggest that the dihydropyridine Ca agonist Bay K 8644 interacts with both voltage-gated and receptor-operated Ca channels and also suggest potential strategies for development of a new class of immunomodulatory drugs.
Young
W
W
Department of Medicine, Stanford University, California.
Chen
J
J
Jung
F
F
Gardner
P
P
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007473:Ion Channels / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects*
D007473:Ion Channels; D001464:Barium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium