Osmosensitive Cl − currents and their relevance to regulatory volume decrease in human intestinal T 8 4 cells: outwardly vs. inwardly rectifying currents

• Published in: The Journal of physiology Vol. 511; no. 1; pp. 45 - 54
• Main Authors: Bond, Tamara D., Ambikapathy, Sujidra, Mohammad, Samira, Valverde, Miguel A.
• Format: Journal Article
• Language: English
• Published: 01-08-1998
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.1998.045bi.x

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.
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.
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.
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.
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.