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 (Vm), 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 1 mM 4-AP, 10 mM TEA, or 200 μM quinine) suppressed NO production. Inhibition of NO production correlated with depolarization of the P388D.1 cell Vm. 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 1 mM 4-AP. The similar effects of K+ channel blockers and L. major on NO production, K+ influx, and Vm suggest that K+ channel activity and the maintenance of Vm is important for NO production in these cells. We suggest that intracellular parasites employ a strategy to inhibit NO production by disrupting Vm during the invasion/infection process by altering host cell K+ channel activity.