Bumetanide inhibition of [CO2 + HCO3]-dependent and -independent equivalent electrical flux in renal cortical thick ascending limbs.
Experiments were performed on single perfused segments of cortical thick ascending limbs of Henle isolated from mouse kidney in order to evaluate the interaction of bumetanide with apical membrane [CO2 + HCO3]-dependent and -independent sodium uptake. In this nephron segment [CO2 + HCO3]-dependent apical membrane salt uptake is accomplished by parallel Na+/H+ and Cl-/HCO3- exchange whereas [CO2 + HCO3]-independent salt uptake results from NaCl cotransport. Tubules were perfused and bathed at 37 degrees C in either [CO2 + HCO3]-buffered solutions (KRB) or with 4-(2-hydroxy(ethyl)-1-piperazineethanesulfonic acid-buffered external media (KRH) at pH 7.4. The spontaneous transepithelial voltage was measured through one-half of a double-barreled perfusion pipette and bipolar d.c. current pulses were delivered through the other half in order to measure the transepithelial conductance (milliSiemens per squared centimeter). The rate of net NaCl absorption was estimated from the electrical flux (Je) and was calculated from the equivalent short-circuit current. Cumulative dose-response data over the range 10(-7) to 10(-4) M luminal bumetanide were obtained in individual tubules in both KRB and KRH solutions. Significant inhibition of transepithelial voltage and Je obtained at 5 X 10(-7) M bumetanide (in KRB) to 10(-6) M (in KRH). When the effect of [CO2 + HCO3] per se on Je was subtracted from the bumetanide-induced inhibition, the two dose-response curves converge.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism / Q000502:physiology*; D001692:Biological Transport / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000502:physiology*; D004232:Diuretics / Q000494:pharmacology*; D004594:Electrophysiology; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects*; D008138:Loop of Henle / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012965:Sodium Chloride / Q000378:metabolism*
D001639:Bicarbonates; D004232:Diuretics; D002034:Bumetanide; D002245:Carbon Dioxide; D012965:Sodium Chloride