Plasma membrane depolarization reduces nitric oxide (NO) production in P388D.1 macrophage-like cells during Leishmania major infection.
In the present study, we compare changes in host cell plasma membrane potential (V(m)), K(+) fluxes, and NO production during K(+) channel blockade with those changes that occur during infection with Leishmania major. Infection of P388D.1 cells with L. major promastigotes or treatment with K(+) channel blockers (either 1mM 4-AP, 10mM TEA, or 200 microM quinine) suppressed NO production. Inhibition of NO production correlated with depolarization of the P388D.1 cell V(m). Infection of P388D.1 cells with L. major increased the unidirectional influx of rubidium (86Rb), a tracer for K(+) flux, that was comparable to that induced by K(+) channel blockade by 1mM 4-AP. The similar effects of K(+) channel blockers and L. major on NO production, K(+) influx, and V(m) suggest that K(+) channel activity and the maintenance of V(m) is important for NO production in these cells. We suggest that intracellular parasites employ a strategy to inhibit NO production by disrupting V(m) during the invasion/infection process by altering host cell K(+) channel activity.
Scott
Kristine D
KD
Department of Biological Sciences, Biological Sciences Building, University of Alberta, Alberta, T6G 2H7, Edmonton, Canada.
Stafford
James L
JL
Galvez
Fernando
F
Belosevic
Miodrag
M
Goss
Greg G
GG
D000818:Animals; D002460:Cell Line; D018320:Leishmania major / Q000502:physiology*; D007941:Leukemia P388; D008264:Macrophages / Q000469:parasitology* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011188:Potassium