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Dihydropyridine Bay K 8644 activates T lymphocyte calcium-permeable channels

W Young, J Chen, F Jung and P Gardner

Department of Medicine, Stanford University, California.

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.

Volume 34, Issue 3, pp. 239-244, 09/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics