ANTIMALARIAL-DRUGS INHIBIT CALCIUM-DEPENDENT BACKWARD SWIMMING AND CALCIUM CURRENTS IN PARAMECIUM-CALKINSI

The antimalarial drugs, quinacrine, chloroquine, quinine, primaquine, and mefloquine, share structural similarities with W-7, a compound tha t inhibits calcium-dependent backward swimming and calcium currents in Paramecium. Therefore, we tested whether antimalarial drugs also inhi bit backward swimming and calcium currents in P. calkinsi. When the Pa ramecium is depolarized in high potassium medium, voltage-dependent ca lcium channels in the ciliary membrane open causing the cell to swim b ackward for 30 to 70 s. Application of calcium channel inhibitors, suc h as W-7, reduce the duration of backward swimming. In 0.05 mM calcium , quinacrine, mefloquine, quinine, chloroquine, primaquine and W-7 all reduced the duration of backward swimming. These effects were seen in sodium-containing and sodium-free high potassium solutions as well as sodium-free depolarizing solutions containing potassium channel block ers. In these low calcium solutions, backward swimming was inhibited b y 50% at concentrations ranging from 100 nM to 30 muM. At higher calci um concentrations (1 mM or 15 mM), the effects of the antimalarials an d W-7 were reduced. The effects of quinacrine and W-7 were tested dire ctly on calcium currents using the two microelectrode voltage clamp te chnique. In 15 mM calcium, 100 muM quinacrine and 100 muM W-7 reduced the peak calcium current by 51% and 42%, respectively. Thus, antimalar ial drugs reduce calcium currents in Paramecium calkinsi.