Couloigner V, Loiseau A, Sterkers O, Amiel C, Ferrary E
INSERM U.426, the Faculté Xavier Bichat, University of Paris 7, France.
Laryngoscope. 1998 Apr;108(4 Pt 1):592-8. doi: 10.1097/00005537-199804000-00024.
In Ménière's disease, an inner ear disorder related to an endolymphatic hydrops, an alteration of the functioning of the endolymphatic sac has been proposed. The endolymphatic sac is assumed to be involved in the secretion/resorption of endolymph. The epithelial transport systems have been indirectly studied by the recording of the endolymphatic sac transepithelial potential (ESP) in control conditions and after the local injection of drugs such as diuretics that have been proposed in the treatment of Ménière's disease. The ESP was recorded, in vivo, in guinea pigs up to 150 minutes after the perisaccular injection of 5 microL of a 150 mmol/L (mM) NaCl solution containing various drugs known to inhibit ionic transport systems. The initial ESP was +8.4+/-0.3 mV (mean +/- SEM, n = 78). The basolateral injection of 5 microL of 150 mM NaCl induced an ESP decrease of 64%+/-6.0% (n = 12), 5 minutes after the end of the injection. Then ESP increased, returning to its initial value at 60 minutes and surpassing it at 120 minutes. Diuretics such as acetazolamide (10[-3] mol/L [M]), an inhibitor of carbonic anhydrase, and amiloride (10[-4] M), an inhibitor of Na channel or Na/H exchanger, decreased the ESP recovery. At variance, bumetanide (10[-6] M, 10[-4] M), the Na-K-Cl cotransport inhibitor, and chlorothiazide (10[-4] M), a Na-Cl cotransporter inhibitor, failed to alter the ESP as compared with the control group. Ouabain (10[-3] M), the Na+,K+-adenosine triphosphatase (ATPase) inhibitor, prevented the ESP recovery otherwise observed 60 minutes after the NaCl injection. Bafilomycin A1, the inhibitor of the vacuolar-type H+-ATPase, prevented the recovery of the ESP with a log-dose/effect (10[-5] M, 10[-6] M, 10[-8] M). Disulfonic acid stilbene (DIDS) (10[-4] M), an inhibitor of transporters involving HCO3-, also prevented the ESP recovery. These results suggest that the genesis of the ESP was highly dependent on acid-base transport systems including carbonic anhydrase, a vacuolar-type H+-ATPase, and an anionic transport system blocked by DIDS. Further studies are needed to confirm the alteration of the acid-base balance in this epithelium and its possible involvement in the pathogenesis of Ménière's disease.
在梅尼埃病（一种与内淋巴积水相关的内耳疾病）中，有人提出内淋巴囊的功能发生了改变。内淋巴囊被认为参与内淋巴的分泌/重吸收。通过记录在对照条件下以及在局部注射利尿剂等用于治疗梅尼埃病的药物后内淋巴囊的跨上皮电位（ESP），对上皮转运系统进行了间接研究。在豚鼠体内，向囊周注射5微升含各种已知可抑制离子转运系统药物的150毫摩尔/升（mM）氯化钠溶液后长达150分钟记录ESP。初始ESP为+8.4±0.3毫伏（平均值±标准误，n = 78）。注射结束5分钟后，向基底外侧注射5微升150 mM氯化钠导致ESP下降64%±6.0%（n = 12）。然后ESP升高，在60分钟时恢复到初始值，并在120分钟时超过初始值。碳酸酐酶抑制剂乙酰唑胺（10[-3]摩尔/升[M]）和钠通道或钠/氢交换体抑制剂阿米洛利（10[-4] M）等利尿剂降低了ESP的恢复。与之不同的是，钠-钾-氯共转运抑制剂布美他尼（10[-6] M，10[-4] M）和钠-氯共转运体抑制剂氯噻嗪（10[-4] M）与对照组相比未能改变ESP。钠、钾-腺苷三磷酸酶（ATP酶）抑制剂哇巴因（10[-3] M）阻止了在注射氯化钠后60分钟时原本会出现的ESP恢复。液泡型氢离子ATP酶抑制剂巴弗洛霉素A1以对数剂量/效应（10[-5] M，10[-6] M，10[-8] M）阻止了ESP的恢复。涉及碳酸氢根的转运体抑制剂二磺基苯乙烯（DIDS）（10[-4] M）也阻止了ESP的恢复。这些结果表明，ESP的产生高度依赖于酸碱转运系统，包括碳酸酐酶、液泡型氢离子ATP酶以及被DIDS阻断的阴离子转运系统。需要进一步研究来证实该上皮中酸碱平衡的改变及其在梅尼埃病发病机制中的可能作用。
