PubMed · 7463959
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
B T Emmerson. 1980. Uricosuric diuretics.. https://doi.org/10.1038/ki.1980.185
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
1. The ion selectivity of a membrane ion conductance that is inactivated by extracellular calcium (Ca2+o) in Xenopus oocytes has been studied using the voltage-clamp technique. 2. The reversal potential of the Ca2+o-sensitive current (Ic) was measured using voltage ramps (-80 to +40 mV) as a function of the external concentration (12-240 mM) of NaCl or KCl. The direction and amplitude of the shifts in reversal potentials are consistent with permeability ratios of 1:0.99:0.24 for K+:Na+:Cl-. 3. Current-voltage (I-V ) relations of Ic, determined during either voltage ramps of 0.5 s duration or at steady state, displayed pronounced rectification at both hyperpolarized and depolarized potentials. However, instantaneous I-V relations showed less rectification and could be fitted by the constant field equation assuming the above K+:Na+:Cl- permeability ratios. 4. Ion substitution experiments indicated that relatively large organic monovalent cations and anions are permeant through Ic channels with the permeability ratios K+:NMDG+:TEA+:TPA+:TBA+:Gluc- = 1:0.45:0. 35:0.2:0.2:0.2. 5. External amiloride (200 microM), gentamicin (220 microM), flufenamic acid (40 microM), niflumic acid (100 microM), Gd3+ (0.3 microM) or Ca2+ (200 microM) caused reversible block of Ic without changing its reversal potential. 6. Preinjection of oocytes with antisense oligonucleotide against connexin 38, the Xenopus hemi-gap-junctional protein, inhibited Ic by 80 % without affecting its ion selectivity, thus confirming and extending the recent suggestion of Ebihara that Ic represents current carried through hemi-gap-junctional channels. 7. In vitro and in vivo maturation of oocytes resulted in a significant decrease in Ic conductance to 7 % and 2 % of control values, respectively. This developmental downregulation of Ic minimizes any toxic effect Ic activation would have when the mature egg is released into Ca2+o-free pond water. 8. The results of this study are discussed in relation to other Ca2+o-inactivated conductances seen in a wide variety of cell types and which have previously been interpreted as arising either from Ca2+o-masked channels or from changes in the ion selectivity of voltage-gated Ca2+ or K+ channels.
Cells within solid tumors are known to exist in a microenvironment that may be acidic and depend on membrane-based mechanisms (Na+/H+ antiport and Na+-dependent Cl-/HCO3- exchanger) that regulate intracellular pH (pHi). We have used the fluorescent pH indicator 2',7'-bis-(2-carboxyethyl) 5 (and 6)-carboxyfluorescein and flow cytometry to study the distribution of pHi and the activity of these pHi-regulating mechanisms among populations of murine mammary sarcoma (EMT6), human breast cancer (MCF-7), and Chinese hamster ovary cells exposed to different levels of extracellular pH (pHe). Cells were exposed to Na+ buffer in the presence or absence of HCO3- and of 5-(N-ethyl-N-isopropyl)-amiloride (a potent inhibitor of the Na+/H+ antiport) to determine the relative importance of each exchanger in the regulation of pHi. Our results indicate that: (a) the distribution of pHi at any value of pHe is broader than can be accounted for by machine noise; (b) cells maintain levels of pHi that are higher than pHe under acidic conditions; (c) the distribution of pHi is narrower when the Na+-dependent Cl-/HCO3- exchanger is active; and (d) populations that are derived from selected cells with values of pHi at lower and higher ends of the pHi distribution generate pHi distributions that are similar to those of controls, suggesting a stochastic variation in the activity of membrane-based mechanisms that regulate pHi. Our data suggest that the Na+-dependent Cl-/HCO3- exchanger is the dominant mechanism for regulation of pHi under moderately acidic conditions such as may occur in the microenvironment of solid tumors.
Single nerve fiber responses to NaCl and their inhibition by amiloride were compared among the chorda tympani (CT) and glossopharyngeal (IXth), and their cross-regenerated nerves in the C57BL/KsJ mice. The CT nerve innervating the anterior part of the tongue contained approximately equal numbers of two types of NaCl-responsive neurons; one type showed strong suppression of NaCl responses by amiloride [amiloride-sensitive (AS) type], and the other type showed only weak or no suppression of NaCl responses by amiloride [amiloride-insensitive (AI) type]. In contrast, the IXth nerve innervating the posterior part of the tongue has almost exclusively the AI type. This relative abundance of the AS and AI types of fibers was not altered by cross-regeneration of the two gustatory nerves into the reverse tongue regions. This suggests that regenerated taste axons selectively recouple with the appropriate type of receptor cell whether they innervate the front or the back of the tongue. Such selective synapse reformation may help explain the stability of response profiles of taste neurons during continual receptor cell turnover.