Antibiotics as tools for studying the electrical properties of tight epithelia

Antibiotics were used as tools for probing the electrical properties of tight epithelia (i.e., epithelia with high electrical resistance). The electrical effects of the polyene antibiotic nystatin were assessed in two mammalian epithelia: the rabbit descending colon and the rabbit urinary bladder. In both tissues, luminal application of the drug increased transepithelial potential and conductance and virtually eliminated apical membrane resistance by increasing permeabilities to Na+, K+, and Cl-. Application of another antibiotic, gramicidin D, produced similar effects on the urinary bladder except that Cl- permeability was unaltered. These effects permitted estimation of apical membrane basolateral membrane, and tight junctional conductances. In addition, a method was developed for assessing active and passive properties of the basolateral membrane. In both the bladder and the colon the membrane behaved basically as a potassium electrode with finite permeabilities for Na+ and Cl-, although an electrogenic Na+ pump was also identified. The existence of this pump was independently verified using ion-sensitive microelectrodes. Recent experiments are consistent with a 3 Na:2 coupling ratio for the pump.