豚鼠输尿管平滑肌细胞内pH的调节：对HCO3-的依赖性

Regulation of intracellular pH in the smooth muscle of guinea-pig ureter: HCO3- dependence.

作者信息

Aickin C C

机构信息

University Department of Pharmacology, Oxford, UK.

出版信息

J Physiol. 1994 Sep 1;479 ( Pt 2)(Pt 2):317-29. doi: 10.1113/jphysiol.1994.sp020298.

DOI:10.1113/jphysiol.1994.sp020298

PMID:7528276

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1155749/

Abstract

HCO3(-)-dependent mechanisms involved in the regulation of intracellular pH (pHi) were characterized using double-barrelled pH-sensitive microelectrodes in smooth muscle cells of the isolated guinea-pig ureter. 2. Removal of external Cl- in the presence of CO2-HCO3- caused a transient alkalosis, consistent with the presence of Cl(-)-HCO3- exchange, before pHi slowly recovered. Recovery from acidosis in the presence of CO2-HCO3- was not affected, at a time when intracellular Cl- would have been maximally depleted, indicating that a counter transport of Cl- and HCO3- was not involved. The recovery was also not affected by amiloride, indicating that Na(+)-H+ exchange was not involved. 3. A transient hyperpolarization was associated with the recovery from acidosis in the presence of CO2-HCO3-, consistent with rheogenic coupling of Na(+)-HCO3- cotransport. However, depolarization caused by elevation of the extracellular potassium (K+o) concentration, which should favour inward transport by the rheogenic mechanism, caused a fall in pHi and decreased the rate of recovery from acidosis. Furthermore, ouabain abolished the transient hyperpolarization without affecting the recovery of pHi. It is concluded that Na(+)-HCO3- cotransport in the ureter is electroneutral. 4. Recovery from acidosis in the presence of CO2-HCO3- was insensitive to DIDS even after prolonged pre-equilibriation and extreme acidosis. The results suggest that Na(+)-HCO3- cotransport in the ureter is insensitive to DIDS and that Cl(-)-HCO3- exchange does not reverse to contribute to the extrusion of acid equivalents. A HCO3- conductance may account for the Na(+)-independent, HCO3(-)-dependent recovery from extreme acidosis. 5. Recovery from experimentally induced alkalosis was inhibited by Cl(-)-free conditions and by DIDS, indicating that Cl(-)-HCO3- exchange was involved. 6. It is concluded that pHi in the smooth muscle of guinea-pig ureter is controlled by three transport mechanisms. By far the most important is an electroneutral Na(+)-HCO3- cotransporter. Na(+)-H+ exchange appears to play little role in the presence of the physiological buffer. Both of these mechanisms extrude acid equivalents and so protect the cell against its fairly substantial intrinsic intracellular acid loading. Cl(-)-HCO3- exchange, on the other hand, is stimulated by intracellular alkalosis to transport acid equivalents into the cell and so restore a more normal pHi.

摘要

利用双管pH敏感微电极，对分离的豚鼠输尿管平滑肌细胞中参与细胞内pH（pHi）调节的HCO₃⁻依赖机制进行了表征。2. 在存在CO₂ - HCO₃⁻的情况下去除细胞外Cl⁻会导致短暂的碱中毒，这与Cl⁻ - HCO₃⁻交换的存在一致，随后pHi缓慢恢复。在细胞内Cl⁻最大程度耗尽时，CO₂ - HCO₃⁻存在下酸中毒的恢复不受影响，这表明Cl⁻和HCO₃⁻的反向转运不参与其中。该恢复也不受氨氯吡咪的影响，表明Na⁺ - H⁺交换不参与。3. 在存在CO₂ - HCO₃⁻的情况下，短暂的超极化与酸中毒的恢复相关，这与Na⁺ - HCO₃⁻共转运的生电偶联一致。然而，细胞外钾（K⁺o）浓度升高引起的去极化，这应该有利于通过生电机制的内向转运，导致pHi下降并降低酸中毒的恢复速率。此外，哇巴因消除了短暂的超极化而不影响pHi的恢复。结论是输尿管中的Na⁺ - HCO₃⁻共转运是电中性的。4. 在存在CO₂ - HCO₃⁻的情况下，即使经过长时间的预平衡和极端酸中毒，酸中毒的恢复对DIDS也不敏感。结果表明，输尿管中的Na⁺ - HCO₃⁻共转运对DIDS不敏感，并且Cl⁻ - HCO₃⁻交换不会反向促进酸当量的排出。HCO₃⁻电导可能解释了从极端酸中毒中不依赖Na⁺、依赖HCO₃⁻的恢复。5. 实验诱导的碱中毒的恢复受到无Cl⁻条件和DIDS的抑制，表明Cl⁻ - HCO₃⁻交换参与其中。6. 结论是豚鼠输尿管平滑肌中的pHi由三种转运机制控制。到目前为止，最重要的是电中性的Na⁺ - HCO₃⁻共转运体。在生理缓冲液存在的情况下，Na⁺ - H⁺交换似乎作用很小。这两种机制都排出酸当量，从而保护细胞免受其相当大量的内在细胞内酸负荷。另一方面，Cl⁻ - HCO₃⁻交换受到细胞内碱中毒的刺激，将酸当量转运到细胞中，从而恢复更正常的pHi。