ISSN:
1432-1424
Keywords:
NaCl transport
;
SITS
;
SCN−
;
DPC
;
Furosemide
;
Verapamil
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
Notes:
Abstract In the rabbit gallbladder epithelium, hydrochlorothiazide (HCTZ) was shown to inhibit the transepithelial NaCl transport and the apical Na+-Cl− symport, to depolarize the apical membrane potential and to enhance the cell-to-lumen Cl− backflux (radiochemically measured), this increase being SITS-sensitive. To better investigate the causes of the depolarization and the Cl− backflux increase, cells were punctured with conventional microelectrodes on the luminal side (incubation in bicarbonate-free saline at 27°C) and the apical membrane potential (V m) was studied either with prolonged single impalements or with a set of short multiple impalements. The maximal depolarization was of 3–4 mV and was reached with 2.5 × 10−4 m HCTZ. It was significantly enhanced by reducing luminal Cl− concentration to 30 mm; it was abolished by SCN−, furosemide, SITS; it was insensitive to DPC. SITS converted the depolarization into a hyperpolarization of about 4 mV; this latter was apamin, nifedipine and verapamil sensitive. It was concluded that HCTZ concomitantly opens apical Cl− and (probably) Ca2+ conductances and, indirectly, a Ca2+-sensitive, apamin inhibitable K+ conductance: since the intracellular Cl− activity is maintained above the value predicted at the electrochemical equilibrium, the opening of the apical Cl− conductance depolarizes V mand enhances Cl− backflux. In the presence of apamin or verapamil, to avoid the hyperpolarizing effects due to HCTZ, the depolarization elicited by this drug was fully developed (7–10 mV) and proved to be Ca2+ insensitive. On this basis and measuring the transepithelial resistance and the apical/basolateral resistance ratio, the Cl− conductance opened by HCTZ has been estimated and the Cl− backflux increase calculated: it proved to be in the order of that observed radiochemically. The importance of this Cl− leak to the lumen in the overall inhibition of the transepithelial NaCl transport by HCTZ has been evaluated.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00233544
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