Changes in cellular membrane and paracellular conductances by amphotericin B in the epithelium of the bullfrog cornea.
In the isolated bullfrog cornea, measurements of DC electrical parameters in conjunction with AC impedance and ultrastructural analyses were used to determine the effects of 10(-5) M amphotericin B on epithelial cellular membrane and paracellular conductances. In NaCl Ringers, amphotericin B elicited a 3.5-fold increase in the specific apical membrane conductance (Ga/Ca); where Ga and Ca are the apical membrane conductance and capacitance, respectively. The basolateral membrane conductance (Gb) and the basolateral membrane capacitance (Cb) fell by 57% and 50%, respectively. In the paracellular pathway, the tight junctional complex (Gj) was unchanged whereas the lateral intercellular space resistance (Rp) decreased by 55%. The declines in Gb and Cb were suggestive of cell volume shrinkage because these changes were consistent with a previously described decline in intracellular K+ content and reduction in exposed basolateral membrane area to current flow. Ultrastructural analysis validated that amphotericin B caused cell volume shrinkage because there was: (1) increased folding of the basolateral membrane and waviness of the basal aspects- of the plasma membrane; (2) dilatation of the lateral intercellular spaces. This agreement suggests that intracellular activity decreased following exposure to amphotericin B which resulted in cell volume shrinkage and an impairment of Cl- uptake across the basolateral membrane.
Reinach
P S
PS
Department of Ophthalmology, Washington University School of Medicine, St. Louis, MO.
Tarvin
J T
JT
Hirsch
M
M
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002712:Chlorides / Q000378:metabolism*; D003315:Cornea / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004553:Electric Conductivity / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005614:Freeze Fracturing; D007365:Intercellular Junctions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008854:Microscopy, Electron; D011892:Rana catesbeiana
D002712:Chlorides; D000666:Amphotericin B