Mutations resulting in resistance to polyene antibiotics decrease voltage-sensitive calcium channel activity in Paramecium.
In this report, the isolation of Paramecium tetraurelia mutants resistant to the polyene antibiotics amphotericin B and filipin are described. These antibiotics are known to specifically interact with membrane sterols to produce a cytotoxic effect. Four mutants resistant to amphotericin B and two mutants resistant to filipin have been isolated. In each case, an individual mutant shows resistance to both amphotericin B and filipin. Genetic analysis indicates that all 6 mutations map to the same complementation group and are not allelic to any of the 3 pawn mutations or to either of the two "barium shy" mutations. The behavioral analysis suggests that these mutations cause an alteration of normal ion channel function. Direct electrophysiological analysis of one mutant indicates mutations to polyene antibiotic resistance cause a specific decrease in voltage-sensitive Ca2+ channel activity.
M
M
Forte
T
T
Hennessey
C
C
Kung
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004351:Drug Resistance; D004594:Electrophysiology; D005372:Filipin / Q000494:pharmacology*; D007473:Ion Channels / Q000502:physiology*; D009154:Mutation; D010247:Paramecium / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D010641:Phenotype; D011090:Polyenes / Q000494:pharmacology*
D007473:Ion Channels; D011090:Polyenes; D000666:Amphotericin B; D005372:Filipin; D002118:Calcium