In a screen for RNA mutagen resistance, we isolated a high fidelity RNA dependent RNA polymerase (RdRp) variant of Coxsackie virus B3 (CVB3). Curiously, this variant A372V is also resistant to amiloride. We hypothesize that amiloride has a previously undescribed mutagenic activity. Indeed, amiloride compounds increase the mutation frequencies of CVB3 and poliovirus and high fidelity variants of...

PURPOSE To investigate the presence of epithelial sodium channels (ENaC) in rabbit and human conjunctival epithelium and to test the effects of topical amiloride, a potassium-sparing diuretic that blocks the ENaC, on tear quantity in rabbits. METHODS Both healthy normal human and rabbit conjunctival tissues underwent immunohistochemistry staining for ENaC-α and γ subunits as well as for rever...

The extent to which endogenously generated nitric oxide alters Na(+) transport across the mammalian alveolar epithelium in vivo has not been documented. Herein we measured alveolar fluid clearance and nasal potential differences in mice lacking the inducible form of nitric oxide synthase [iNOS; iNOS(-/-)] and their corresponding wild-type controls [iNOS(+/+)]. Alveolar fluid clearance values in...

TO THE EDITOR: In a recent review, O’Brodovich et al. (7) analyzed experimental evidence for the significance of amiloride-insensitive alveolar epithelial sodium transport in the mammalian lung. In a recent observational study of epithelial ion transport in children with meningococcal septicemia-induced pulmonary edema, indirect evidence of a systemic reduction in epithelial sodium transport as...

In nephrotic syndrome, aberrant glomerular filtration of plasminogen and conversion to active plasmin in preurine are thought to activate proteolytically epithelial sodium channel (ENaC) and contribute to sodium retention and edema. The ENaC blocker amiloride is an off-target inhibitor of urokinase-type plasminogen activator (uPA) in vitro. It was hypothesized that uPA is abnormally filtered to...

The volume of individual cells in intact frog urinary bladders was determined by quantitative microscopy and changes in volume were used to monitor the movement of solute across the basolateral membrane. When exposed to a serosal hyposmotic solution, the cells swell as expected for an osmometer, but then regulate their volume back to near control in a process that involves the loss of KCl. We s...

The large-conductance, calcium-activated BK-α/β4 potassium channel, localized to the intercalated cells of the distal nephron, mediates potassium secretion during high-potassium, alkaline diets. Here we determine whether BK-α/β4-mediated potassium transport is dependent on epithelial sodium channel (ENaC)-mediated sodium reabsorption. We maximized sodium-potassium exchange in the distal nephron...

The activity of taste cells maintained in the intact hamster tongue was monitored in response to acid stimulation by recording action currents from taste receptor cells with an extracellular "macro" patch pipette: a glass pipette was pressed over the taste pore of fungiform papillae and perfused with citric acid, hydrochloric acid, or NaCl. Because this technique restricted stimulus application...

Noise analysis of the Na+ channels of the apical membranes of frog skin bathed symmetrically in a Cl-HCO3 Ringer solution was done with amiloride and CGS 4270. Tissues were studied in their control states and after inhibition of transepithelial Na+ transport (Isc) by addition of quinine or quinidine to the apical solution. A critical examination of the amiloride-induced noise indicated that the...

Behavioral and physiological studies have demonstrated a reduced sensitivity to several taste stimuli early in development. It has been suggested that this reduced sensitivity results from a late maturation of underlying transduction mechanisms. Little is known, however, about maturation of membrane properties of taste cells early in development. We have obtained whole-cell recordings from sing...