VOLUME-SENSITIVE ANION CHANNELS MEDIATE SWELLING-ACTIVATED INOSITOL AND TAURINE EFFLUX
VOLUME-SENSITIVE ANION CHANNELS MEDIATE SWELLING-ACTIVATED INOSITOL AND TAURINE EFFLUX
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DOI：
10.1152/ajpcell.1993.265.6.c1489
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发表时间：
1993-12-01
影响因子：
--
通讯作者：
STRANGE, K
中科院分区：
文献类型：
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作者：
JACKSON, PS;STRANGE, K
C6 神经胶质瘤细胞积累有机渗透剂肌醇以应对慢性高渗应激。恢复等渗条件后，细胞肿胀激活不依赖 Na+ 的被动低亲和力肌醇流出机制，该机制可被多种阴离子转运阻滞剂、某些脂氧合酶阻滞剂和各种多不饱和脂肪酸抑制 80-100%。细胞肿胀也会增强牛磺酸的流出。牛磺酸流出途径具有与肌醇流出机制相同的特征，包括激活和失活动力学、渗透敏感性、药理学敏感性以及某些Na+和Cl-替代物的抑制。这些结果强烈表明体积敏感的肌醇和牛磺酸流出是由共同的转运机制介导的。阴离子转运阻滞剂和不饱和脂肪酸对转运途径的抑制间接表明这些溶质的流出可能是由阴离子通道介导的。使用 CsCl 溶液中的全细胞膜片钳测量来检验这一假设。在高渗条件下，C6 细胞具有极低的膜电导（约 0.02 nS/pF）。然而，细胞肿胀后，全细胞阴离子电导迅速激活至高达 1.5-2 nS/pF 的值。这种电导是向外整流的并且对阴离子具有选择性，并且被肿胀激活的肌醇和牛磺酸流出的阻滞剂抑制80-100%。电导的相对牛磺酸渗透性(即P(牛磺酸)/P(Cl))为0.20。用肌醇或山梨醇等渗替代外部介质中的棉子糖诱导瞬时内向电流，表明 Cl- 和这些多元醇竞争通道上的共同结合位点。我们得出的结论是，体积敏感的阴离子通道介导结构多样的有机渗透剂（例如牛磺酸和肌醇）从细胞中流出。
C6 glioma cells accumulate the organic osmolyte inositol in response to chronic hypertonic stress. Upon return to isotonic conditions, cell swelling activates a Na+-independent passive low-affinity inositol efflux mechanism that is inhibited 80-100% by a number of anion transport blockers, certain lipoxygenase blockers, and various polyunsaturated fatty acids. Taurine efflux is also enhanced by cell swelling. The taurine efflux pathway has characteristics that are identical to those of the inositol efflux mechanism, including kinetics of activation and inactivation, osmotic sensitivity, pharmacological sensitivity, and inhibition by certain Na+ and Cl- substitutes. These results suggest strongly that volume-sensitive inositol and taurine efflux are mediated by a common transport mechanism. The inhibition of the transport pathway by anion transport blockers and unsaturated fatty acids suggests indirectly that efflux of these solutes may be mediated by an anion channel. Whole cell patch clamp measurements in CsCl solutions were used to test this hypothesis. Under hypertonic conditions, C6 cells had an extremely low membrane conductance (approximately 0.02 nS/pF). After cell swelling, however, whole cell anion conductance was activated rapidly to values up to 1.5-2 nS/pF. This conductance was outwardly rectified and selective for anions and was inhibited 80-100% by blockers of swelling-activated inositol and taurine efflux. The relative taurine permeability (i.e., P(taurine)/P(Cl)) of the conductance was 0.20. Isosmotic replacement of raffinose in the external medium with inositol or sorbitol induced a transient inward current, suggesting that Cl- and these polyols compete for common binding sites on the channel. We conclude that a volume-sensitive anion channel mediates the efflux of structurally diverse organic osmolytes such as taurine and inositol from the cell.