Referenced in: none

Automatically associated channels: ClC3 , ClC4

Title: Interaction between Cl- channels and CRAC-related Ca2+ signaling during T lymphocyte activation and proliferation.

Authors: Guan-Lei Wang, Yan Qian, Qin-Ying Qiu, Xiu-Jian Lan, Hua He, Yong-Yuan Guan

Journal, date & volume: Acta Pharmacol. Sin., 2006 Apr , 27, 437-46

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16539844

Abstract
To test the hypothesis that Cl channel blockers affect T cell proliferation through Ca2+-release-activated Ca2+ (CRAC) signaling and examine the effects of the combination of a CRAC channel blocker and a Cl channel blocker on concanavalin A (ConA; 5 mg/mL)-induced Ca2+ signaling, gene expression and cellular proliferation in human peripheral T lymphocytes.[3H]Thymidine incorporation, Fura-2 fluorescent probe, RNase protection assay, and reverse transcription-polymerase chain reaction were used.The Cl channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) inhibited ConA-induced Ca2+ influx, interleukin-2 mRNA expression and T lymphocyte proliferation in a concentration-dependent manner, and also enhanced the inhibitory effects of 1-[beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenethyl]-1H-imidazole (SK&F96365) on the above key events during T cell activation. A combination of DIDS (1 micromol/L) and SK&F96365 (1 micromol/L) significantly diminished ConA-induced ClC-3 mRNA expression by 64%, whereas DIDS(1 micromol/L) or SK&F96365 (1 micromol/L) alone decreased ConA-induced ClC-3 mRNA expression by only 16% and 9%, respectively.These results suggest that there is an interaction between CRAC-mediated Ca2+ signaling and DIDS-sensitive Cl channels during ConA-induced T cell activation and proliferation. Moreover, the DIDS-sensitive Cl channels may be related to the ClC-3 Cl channels.