Human natural killer cells express Na+ channels. A pharmacologic flow cytometric study.
Voltage-gated excitability of purified human NK cells was studied by using flow cytometry and the voltage-sensitive dye, oxonol. Highly purified human NK cells (CD16 = 95 +/- 1%) from normal volunteers were prepared by using a negative panning technique. The Na(+)-channel agonists batrachotoxin (BTX) (1 to 4 microM) and veratridine (Ver) (100 to 400 microM) depolarized a population of highly purified human NK cells as determined by flow cytometry. BTX and Ver responses were concentration-, time-, temperature-, and Na(+)-dependent. The Na+ channel antagonist tetrodotoxin (1 microM) blocked BTX and Ver responses. Ver (100 microM) produced significant inhibition of cytotoxicity when purified NK cells were incubated with K562 tumor target cells in a 4-h 51Cr release cytotoxicity assay. The effect was blocked by tetrodotoxin. These results strongly suggest presence of functional Na+ channels in NK cells. Activation of voltage-dependent Na+ channels depolarizes cells and reduces their in vitro cytotoxic function.
Mandler
R N
RN
Department of Neurology, University of New Mexico School of Medicine, Albuquerque 87131.
Seamer
L C
LC
Whitlinger
D
D
Lennon
M
M
Rosenberg
E
E
Bankhurst
A D
AD
D001496:Batrachotoxins / Q000494:pharmacology; D002469:Cell Separation; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D001496:Batrachotoxins; D015222:Sodium Channels; D013779:Tetrodotoxin; D014701:Veratridine