Modulation of polymyxin B effects on mammalian urinary bladder.
This report demonstrates that Ca2+, Mg2+, and protons alter the ability of polymyxin B (PX, a cationic antibiotic used clinically as a bactericidal agent) to increase the apical membrane conductance of the rabbit urinary bladder. Using electrophysiological methods, we determine that these alterations occur by two mechanisms. First, they blocked the PX-induced conductance in a rapid and reversible manner; second, they competed with PX for a membrane binding site. In addition, Ca2+ (but not Mg2+ or protons) altered the rate at which the induced conductance could be reversed. When solution pH was greater than 8.8, PX was not able to induce a conductance. This ability of high pH to inhibit the action of PX was due to a decrease in the number of positive charges on PX. Further studies demonstrated that for maximal activity, PX required its fatty acid tail. These data were used to develop a model describing the mechanism by which PX can induce a conductance in the apical membrane of the rabbit urinary bladder.
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77555, USA.
J R
JR
Berg
C M
CM
Spilker
S A
SA
Lewis
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D004553:Electric Conductivity; D004594:Electrophysiology / Q000379:methods; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008322:Mammals; D008433:Mathematics; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D011112:Polymyxin B / Q000494:pharmacology*; D011817:Rabbits; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
D008274:Magnesium; D011112:Polymyxin B; D002118:Calcium