Kinetic analysis of K+ ion channel function in lymphokine-activated killer (LAK) cells.
K+ ion channels of lymphocytes have been implicated in cellular differentiation, activation and cytolytic functions. We previously demonstrated that K+ channel blockers modulate lytic activity of CTLs and LAK cells. In the present study, we define and quantitate the inhibitory effects of ion channel blockers on the lytic process using kinetic analysis of lysis. The K+ channel blocker, 4-aminopyridine, the neuroendocrine monoamine, serotonin, its agonist, quipazine, and the Ca++ dependent K+ channel blocker, quinidine were found to non-competitively inhibit the lytic process in a dose-dependent manner. These compounds inhibit lytic activity by causing a decrease in the maximum velocity (Vmax) by which LAK cells lyse tumor targets. These ion channel blockers did not alter effector or target cell viability or the binding of LAK cells to tumor cells. The inhibitory effects occurred at the effector cell level, since preincubation of LAK effector cells resulted in a dose-dependent decrease in Vmax which was related to a slower rate of target cell lytic programming (k2) by the LAK effector cells. Modulation of LAK cell lytic function occurs at a post-binding step, perhaps in the generation or release of the lytic signal.
LeFever
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Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226.
Liepins
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D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D066298:In Vitro Techniques; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011802:Quinidine / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology
D015221:Potassium Channels; D012701:Serotonin; D011814:Quipazine; D015761:4-Aminopyridine; D011802:Quinidine