Premium
Osmosensitive Cl − currents and their relevance to regulatory volume decrease in human intestinal T 8 4 cells: outwardly vs. inwardly rectifying currents
Author(s) -
Bond Tamara D.,
Ambikapathy Sujidra,
Mohammad Samira,
Valverde Miguel A.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.045bi.x
Subject(s) - dids , hyperpolarization (physics) , chemistry , membrane potential , medicine , biophysics , endocrinology , biology , biochemistry , membrane , stereochemistry , nuclear magnetic resonance spectroscopy
1 The swelling‐activated outwardly rectifying Cl − current (I Cl(swell) ) recorded in T 8 4 human intestinal cells was completely blocked by 10 μM tamoxifen, while 300 μM Cd 2+ had no effect. 2 A ClC‐2‐like, inwardly rectifying Cl − current was activated after strong hyperpolarization in T 8 4 cells. This current was completely inhibited by 300 μM Cd 2+ , unaffected by 10 μM 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 T 8 4 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 T 8 4 cells. Tamoxifen (10 μM), 1,9‐dideoxyforskolin (DDFSK; 100 μM) and 4,4′‐diisothiocyanatostilbene‐2,2′‐disulphonic acid (DIDS; 100 μM) blocked RVD while 300 μM Cd 2+ had no effect upon RVD following a 30 % hyposmotic shock. The RVD response was similarly unaffected by Cd 2+ 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 T 8 4 cells is the tamoxifen‐, DDFSK‐ and DIDS‐sensitive I Cl(swell) and not the hyperpolarization‐activated, Cd 2+ ‐sensitive Cl − current associated with the ClC‐2 Cl − channel.