Arachidonic acid-induced activation of large-conductance potassium channels and membrane hyperpolarization in mouse B cells.
Lymphocytes express voltage-gated (Kv) and Ca(2+)-activated (IKCa1) K(+) channels. Recently, we found that WEHI-231, an immature B cell line, expresses voltage-independent K(+) channels called large-conductance background K( + ) channels (LK(bg)). Arachidonic acid (AA) has attracted attention because of its potential regulatory roles in the apoptosis of immature B cells. To elucidate the functional targets of AA, we investigated the effects of AA on membrane currents, voltages, and cytoplasmic Ca(2+) concentration ([Ca(2+)](c)) of WEHI-231 and Bal-17 cells that represent immature and mature mouse B cells, respectively. In whole-cell patch clamp, both Kv and IKCa1 were inhibited by AA. On the other hand, AA activated LK(bg) current and non-selective cationic (NSC) current in WEHI-231 while only NSC current in Bal-17. Inside-out patch clamp study showed that AA directly activates LK(bg). AA induced hyperpolarization of WEHI-231 and depolarization of Bal-17 cells, respectively. The selective functional expression of LK(bg) and their activation by AA were also confirmed in the immature B cells (B220(+)/AA4.1(+)) freshly isolated from mouse spleen. In fura-2 spectrofluorimetry, AA induced persistent increase in [Ca(2+)](c) of WEHI-231 cells, which was attenuated by KCl-induced depolarization. In Bal-17 cell, however, AA induced only a transient increase of [Ca(2+)](c). In summary, the novel type of background K(+) channels (LK(bg)) in immature B cells is strongly activated while the other K(+) channels (Kv and IKCa1) commonly expressed in lymphocytes are inhibited by AA. The hyperpolarization and augmentation of Ca(2+) influx by LK(bg) activation might play a role in the response of immature B cells to AA.
Zheng
Haifeng
H
Department of Physiology, Seoul National University College of Medicine, 28 Yongon-dong, Chongro-gu, Seoul, 110-799, South Korea.
Nam
Joo Hyun
JH
Nguen
Yen Hoang
YH
Kang
Tong Mook
TM
Kim
Tae Jin
TJ
Earm
Yung E
YE
Kim
Sung Joon
SJ
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002460:Cell Line; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*
D015221:Potassium Channels; D016718:Arachidonic Acid; D002118:Calcium