PubMed 25305321

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNK3 , KCNK5

Title: HIF-1α-mediated upregulation of TASK-2 K⁺ channels augments Ca²⁺ signaling in mouse B cells under hypoxia.

Authors: Dong Hoon Shin, Haiyue Lin, Haifeng Zheng, Kyung Su Kim, Jin Young Kim, Yang Sook Chun, Jong Wan Park, Joo Hyun Nam, Woo Kyung Kim, Yin Hua Zhang, Sung Joon Kim

Journal, date & volume: J. Immunol., 2014 Nov 15 , 193, 4924-33

PubMed link:

The general consensus is that immune cells are exposed to physiological hypoxia in vivo (PhyO2, 2-5% P(O2)). However, functional studies of B cells in hypoxic conditions are sparse. Recently, we reported the expression in mouse B cells of TASK-2, a member of pH-sensitive two-pore domain K(+) channels with background activity. In this study, we investigated the response of K(+) channels to sustained PhyO2 (sustained hypoxia [SH], 3% P(O2) for 24 h) in WEHI-231 mouse B cells. SH induced voltage-independent background K(+) conductance (SH-K(bg)) and hyperpolarized the membrane potential. The pH sensitivity and the single-channel conductance of SH-K(bg) were consistent with those of TASK-2. Immunoblotting assay results showed that SH significantly increased plasma membrane expressions of TASK-2. Conversely, SH failed to induce any current following small interfering (si)TASK-2 transfection. Similar hypoxic upregulation of TASK-2 was also observed in splenic primary B cells. Mechanistically, upregulation of TASK-2 by SH was prevented by si hypoxia-inducible factor-1α (HIF-1α) transfection or by YC-1, a pharmacological HIF-1α inhibitor. In addition, TASK-2 current was increased in WEHI-231 cells overexpressed with O2-resistant HIF-1α. Importantly, [Ca(2+)]c increment in response to BCR stimulation was significantly higher in SH-exposed B cells, which was abolished by high K(+)-induced depolarization or by siTASK-2 transfection. The data demonstrate that TASK-2 is upregulated under hypoxia via HIF-1α-dependent manner in B cells. This is functionally important in maintaining the negative membrane potential and providing electrical driving force to control Ca(2+) influx.