Stoddard J S, Altenberg G A, Ferguson M L, Reuss L
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77550.
Am J Physiol. 1990 Jun;258(6 Pt 1):C1150-8. doi: 10.1152/ajpcell.1990.258.6.C1150.
In Necturus gallbladders bathed in a NaCl Ringer solution buffered with 10 mM HCO3(-)-1% CO2, furosemide (added to the serosal solution) caused a concentration-dependent hyperpolarization of both cell membranes that was slow and reversible. At 10(-3) M furosemide, the basolateral membrane voltage (Vcs) increased significantly from -71 +/- 3 to -85 +/- 3 mV, the depolarization of Vcs elicited by a 10-fold rise in serosal [K+] increased from 34 +/- 4 to 50 +/- 1 mV, the depolarization elicited by lowering serosal [Cl-] from 98 to 8.1 mM was reduced from 15 +/- 1 to 1 +/- 1 mV, and the depolarization in response to lowering serosal [HCO3-] from 10 to 1 mM was reduced from 13 +/- 1 to 5 +/- 0.4 mV. Furosemide could in principle decrease the basolateral membrane Cl- conductance (Gcl), increase the basolateral membrane K+ conductance, or have a combined effect. To distinguish among these possibilities, we estimated the resistance of the basolateral membrane (Rb) by means of two-point intraepithelial cable analysis experiments. Furosemide increased Rb by 22%, which indicates that furosemide reduces basolateral membrane Gcl. The effect cannot be attributed to inhibition of apical membrane anion exchange by serosal addition of furosemide, because base secretion from cells to lumen is unchanged. We conclude that furosemide blocks reversibly basolateral membrane electrodiffusive Cl- permeability. A concomitant stimulation of basolateral membrane electrodiffusive K+ permeability is also possible.
在浸泡于用10 mM HCO₃⁻-1% CO₂缓冲的NaCl林格溶液中的美西螈胆囊中，呋塞米（添加到浆膜溶液中）导致两个细胞膜出现浓度依赖性超极化，这种超极化缓慢且可逆。在10⁻³ M呋塞米作用下，基底外侧膜电压（Vcs）从-71±3 mV显著增加到-85±3 mV，浆膜[K⁺]升高10倍引起的Vcs去极化从34±4 mV增加到50±1 mV，浆膜[Cl⁻]从98 mM降低到8.1 mM引起的去极化从15±1 mV降低到1±1 mV，响应浆膜[HCO₃⁻]从10 mM降低到1 mM的去极化从13±1 mV降低到5±0.4 mV。呋塞米原则上可以降低基底外侧膜Cl⁻电导（Gcl）、增加基底外侧膜K⁺电导，或者产生联合效应。为了区分这些可能性，我们通过两点上皮内电缆分析实验估计基底外侧膜电阻（Rb）。呋塞米使Rb增加了22%，这表明呋塞米降低了基底外侧膜Gcl。该效应不能归因于通过在浆膜添加呋塞米对顶端膜阴离子交换的抑制，因为从细胞到管腔的碱分泌没有变化。我们得出结论，呋塞米可逆地阻断基底外侧膜的电扩散Cl⁻通透性。同时刺激基底外侧膜的电扩散K⁺通透性也是可能的。
