Antimalarial drugs inhibit calcium-dependent backward swimming and calcium currents in Paramecium calkinsi

Abstract

The antimalarial drugs, quinacrine, chloroquine, quinine, primaquine, and mefloquine, share structural similarities with W-7, a compound that inhibits calcium-dependent backward swimming and calcium currents in Paramecium . Therefore, we tested whether antimalarial drugs also inhibit backward swimming and calcium currents in P. calkinsi . When the Paramecium is depolarized in high potassium medium, voltage-dependent calcium channels in the ciliary membrane open causing the cell to swim backward for 30 to 70 s. Application of calcium channel inhibitors, such 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 blockers. In these low calcium solutions, backward swimming was inhibited by 50% at concentrations ranging from 100 n M to 30 μ M . At higher calcium concentrations (1 m M or 15 m M ), the effects of the antimalarials and W-7 were reduced. The effects of quinacrine and W-7 were tested directly on calcium currents using the two microelectrode voltage clamp technique. In 15 mM calcium, 100 μ M quinacrine and 100 μM W-7 reduced the peak calcium current by 51% and 42%, respectively. Thus, antimalarial drugs reduce calcium currents in Paramecium calkinsi .