Toxic effects of antimalarial drugs in Paramecium: role of calcium channels.
The antimalarial drugs, quinacrine, quinine and mefloquine, as well as the structurally-similar compound, W-7, inhibit calcium-dependent backward swimming and calcium currents in Paramecium calkinsi. These drugs are also toxic to paramecia at high concentrations. Therefore, one site of toxic action of the drugs may be the calcium channel. To test this hypothesis, the toxicity of the antimalarials and W-7 was compared in paramecia with and without calcium channels. Since calcium channels are located on the cilia, calcium channels were removed from the paramecia by deciliating the cells. Deciliated cells were found to be less susceptible to the lethal effects of the antimalarials and W-7 than their ciliated counterparts. Moreover, Pawns, mutants of P. tetraurelia that possess cilia but lack functional calcium channels, were also less susceptible to the antimalarials than wild-type cells. Thus, calcium channels may be one site of toxic action of the antimalarial drugs in paramecia and perhaps in other protists.
Nori
V S
VS
Department of Biological Sciences, Mount Holyoke College, South Hadley, MA 01075, USA.
Barry
S R
SR
D000818:Animals; D000962:Antimalarials / Q000506:poisoning*; D015220:Calcium Channels / Q000502:physiology*; D002498:Centrifugation; D002923:Cilia / Q000648:ultrastructure; D004351:Drug Resistance; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology; D009154:Mutation; D010247:Paramecium / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure
D000962:Antimalarials; D015220:Calcium Channels; D000431:Ethanol