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PubMed · 9679162

Osmosensitive C1- currents and their relevance to regulatory volume decrease in human intestinal T84 cells: outwardly vs. inwardly rectifying currents.

T D Bond·S Ambikapathy·S Mohammad·M A Valverde
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Abstract

1. The swelling-activated outwardly rectifying Cl- current (ICl(swell)) recorded in T84 human intestinal cells was completely blocked by 10 microM tamoxifen, while 300 microM Cd2+ had no effect. 2. A ClC-2-like, inwardly rectifying Cl- current was activated after strong hyperpolarization in T84 cells. This current was completely inhibited by 300 microM Cd2+, unaffected by 10 microM tamoxifen, and its magnitude increased slightly in response to cell swelling under hyposmotic conditions. However, the swelling-dependent modulation occurred only after prior activation by hyperpolarizing voltages. 3. T84 cells behaved initially close to perfect osmometers in response to changes in external osmolalities between +20 and -30 %. The cells underwent full regulatory volume decrease (RVD) within 16 min when exposed to 30 or 10 % hyposmotic shocks. 4. Pharmacological tools were used to determine the anionic pathway(s) involved in RVD in T84 cells. Tamoxifen (10 microM), 1,9-dideoxyforskolin (DDFSK; 100 microM) and 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS; 100 microM) blocked RVD while 300 microM Cd2+ had no effect upon RVD following a 30 % hyposmotic shock. The RVD response was similarly unaffected by Cd2+ when cells were exposed to a smaller (10 %) hyposmotic shock. 5. In conclusion, these data show that the anionic pathway primarily activated by cell swelling and relevant to RVD in T84 cells is the tamoxifen-, DDFSK- and DIDS-sensitive ICl(swell) and not the hyperpolarization-activated, Cd2+-sensitive Cl- current associated with the ClC-2 Cl- channel.

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4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidCLC-2 Chloride ChannelsCadmiumCell LineChloride ChannelsColforsinColonic NeoplasmsHumansHypertonic SolutionsHypotonic SolutionsIntestinal MucosaMembrane PotentialsNerve Tissue ProteinsOsmolar ConcentrationTamoxifenTumor Cells, CulturedJournal ArticleResearch Support, Non-U.S. Gov't

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T D Bond, S Ambikapathy, S Mohammad, M A Valverde. 1998-08-15. Osmosensitive C1- currents and their relevance to regulatory volume decrease in human intestinal T84 cells: outwardly vs. inwardly rectifying currents.. https://doi.org/10.1111/j.1469-7793.1998.045bi.x

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